{"publication_id":"145fcccc-2360-4120-8674-34dd3e97ade7","traces":[{"claim_id":"claim_1","claim":"Evidence-honesty note: The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims. Aspirin remains one of the most widely used medications globally, yet its effects beyond cardiovascular prophylaxis — including on cancer incidence and survival, infection-related mortality, and aging-relevant outcomes — remain actively debated as guidelines shift and observational cohorts proliferate. We conducted an AI-assisted structured evidence synthesis across 55 curated reference papers indexed for Aspirin, extracting effect estimates, confidence intervals, and p-values into an audit-trailed evidence table while preserving the design and directness annotations supplied by the original sources. For COVID-19, pooled analyses of hospitalized patients indicated that aspirin use was independently associated with reduced in-hospital mortality (P = 0.007), mechanical ventilation, and ICU admission, although a parallel meta-analysis limited to randomized controlled trials found no statistically significant effect on all-cause mortality. Safety signals include increased intracerebral hemorrhage when aspirin was combined with severe hypertension (P = 0.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_2","claim":"Evidence-honesty note: The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_3","claim":"We conducted an AI-assisted structured evidence synthesis across 55 curated reference papers indexed for Aspirin, extracting effect estimates, confidence intervals, and p-values into an audit-trailed evidence table while preserving the design and directness annotations supplied by the original sources.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_4","claim":"Safety signals include increased intracerebral hemorrhage when aspirin was combined with severe hypertension (P = 0.003), whereas aspirin exposure was associated with lower severe AKI incidence in MIMIC-IV/eICU sepsis cohorts (P < 0.001), illustrating outcome- and population-dependent benefit–risk tradeoffs.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_5","claim":"Across outcome classes, cross-study disagreements emerged in the synthesis — most prominently null-versus-positive conflicts on contextual outcomes (Sun 2019 vs Alabsi 2023; Wang 2021a vs Huff 2025) and on longevity outcomes in specific subgroups (Wu 2024, Xu 2026, Chow 2022 vs Celik 2018) — confirming that aspirin's effect profile is context-dependent rather than uniformly beneficial.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_6","claim":"Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_7","claim":"This synthesis evaluates evidence on aspirin use effects across 55 included source papers and 2311 high-confidence extracted claims. The review is organized around the distinction between direct interventional hard-endpoint evidence, adjacent/review/context evidence, and mechanistic evidence so that biological plausibility is not confused with clinical certainty.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_8","claim":"The corpus contains no sources classified primarily as direct interventional hard-endpoint evidence, 55 adjacent, review, or context sources, and no sources classified primarily as mechanistic or model-system evidence. That distribution makes the synthesis appropriate for evaluating convergence, boundary conditions, and trial-design implications, while requiring caution around any conclusion that would exceed the direct human evidence.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_9","claim":"The introductory frame therefore treats the corpus as a set of evidence roles rather than a single directional verdict. Direct sources define the applied boundary, adjacent sources locate comparable clinical contexts, and mechanistic sources identify plausible bridges that still require endpoint-level confirmation.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_10","claim":"This distinction matters for publication because it makes the paper falsifiable. A future source can strengthen, weaken, or reverse the synthesis by changing the evidence tier, direction, or outcome-class balance.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_11","claim":"The mechanistic layer is most useful when it explains why a trial signal might appear or fail to appear. It is weaker when it is used as a replacement for outcome data, so this synthesis treats it as interpretive support rather than independent clinical proof.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_12","claim":"Null findings have a specific role in this evidence model. They do not erase mechanistic plausibility, but they do narrow the set of claims that can be made about effect consistency, target population, and endpoint selection.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_13","claim":"Adverse or negative signals are likewise retained in the main interpretation. For an aging intervention, the risk profile is part of the efficacy question because a plausible mechanism is not sufficient if the same corpus shows offsetting harm or tolerability constraints.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_14","claim":"The evidence base also distinguishes breadth from certainty. A broad corpus can cover many biological domains while still leaving the clinically decisive question unresolved if direct evidence is limited, heterogeneous, or endpoint-specific.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_15","claim":"For that reason, the manuscript does not collapse every source into a single recommendation. It presents the intervention as a set of linked claims whose strength depends on the evidence tier and the match between mechanism, population, and endpoint.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_16","claim":"The research value of the synthesis lies in making these boundaries explicit. It identifies which evidence streams are already aligned, which ones remain discordant, and which future studies would most directly test the unresolved bridge.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_17","claim":"The background evidence for aspirin use effects is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as the retained evidence base are interpreted separately from mechanistic studies such as the retained evidence base, because these evidence roles answer different questions about aging biology and clinical translation.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_18","claim":"The direct evidence establishes what has been observed in human or adjacent clinical settings. The mechanistic evidence helps explain why an effect might be plausible, but it does not by itself establish the size, durability, or safety of a human healthspan effect.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_19","claim":"Across the retained sources, positive signals cluster around the longevity, contextual adjacent evidence, safety and comorbidity outcome classes; null signals around the contextual adjacent evidence, deficiency prevalence and cardiometabolic outcome classes; and negative or adverse signals around no dominant outcome class. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_20","claim":"The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_21","claim":"The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, observed direct signals when present, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_22","claim":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias sidecar when populated, and claim registry) rather than from re-parsed full text.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_23","claim":"Risk-of-bias framework assignment follows study design (RoB-2 for RCTs, ROBINS-I for non-randomised studies, AMSTAR-2 for systematic reviews / meta-analyses). Public appraisal claims are limited to populated `risk_of_bias.json` rows; when no populated ratings are present, interpretation remains bounded by source tier and directness rather than formal RoB certification.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_24","claim":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, dosing and pharmacokinetics, immune and inflammation, longevity, mortality and survival, safety and comorbidity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_25","claim":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_26","claim":"Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_27","claim":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_28","claim":"| Aspirin Use Effects / Contextual Adjacent Evidence | n=23; claims=984 | significant source statistic in 16/23 sources; receipt-level direction coded unclear | 14 indirect; 9 review | limited corpus depth in this outcome class |","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_29","claim":"| Aspirin Use Effects / Cardiometabolic | n=1; claims=81 | significant source statistic in 1/1 sources; receipt-level direction coded null | 1 indirect | single-source slice; hypothesis-generating |","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_30","claim":"Contextual Adjacent Evidence: n=23; claims=984; mixed signal in 15/23 sources | directness: 14 indirect; 9 review; main limitation: no direct clinical anchor.","citation_support":[],"candidate_sources":[{"study":"Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis","year":2020,"doi":"10.1186/s12885-020-07117-4","url":"https://doi.org/10.1186/s12885-020-07117-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review","cited_as":"Lin 2020","excerpt":"BACKGROUND: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"An Evaluation of Aspirin Treatment Preferences of Physicians in Hypertensive Patients in Terms of Current Guidelines: A Subgroup Analysis of the ASSOS Trial in Turkey","year":2022,"doi":"10.5152/AnatolJCardiol.2021.541","url":"https://doi.org/10.5152/AnatolJCardiol.2021.541","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Sancar 2022","excerpt":"BACKGROUND: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial has been the largest study ever conducted among patients in Turkey regarding aspirin treatment. In the subgroup analysis of the hypertensive group of the Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial, we aimed to evaluate the physicians' adherence to current guidelines regarding their aspirin treatment preferences. METHODS: The Appropriateness of Aspirin Use in Medical Outpatients: A Multicenter, Observational Study trial is a cross-sectional and multicenter study conducted among 5007 consecutive patients aged ≥18 years. The study population consisted of outpatients on aspirin treatment (80-300 mg). The patient data were obtained from 30 different cardiology clinics of 14 cities from all over Turkey. In this subgroup analysis, patients were divided into 2 groups: the hypertensive group (n=3467, 69.3%) and the group without hypertension (n=1540, 30.7%) according to the 2018 European Society of Cardiology/ European Society of Hypertension Guidelines for the Management of Arterial Hypertension.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment","year":2021,"doi":"10.3389/fonc.2021.633462","url":"https://doi.org/10.3389/fonc.2021.633462","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Fan 2021","excerpt":"Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa ( P =0.175).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19","year":2022,"doi":"10.1001/jamanetworkopen.2022.3890","url":"https://doi.org/10.1001/jamanetworkopen.2022.3890","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Chow 2022","excerpt":"IMPORTANCE: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. OBJECTIVE: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). EXPOSURE: Aspirin use within the first day of hospitalization. MAIN OUTCOME AND MEASURES: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival","year":2025,"doi":"10.1038/s41523-025-00775-2","url":"https://doi.org/10.1038/s41523-025-00775-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Peng 2025","excerpt":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","source_id":"source_5","support_kind":"candidate_source_row"}]}]}