{"publication_id":"f1b39b71-2cc3-43a3-ab5a-287574699c7d","traces":[{"claim_id":"claim_1","claim":"This paper synthesizes evidence on Statin across 62 accepted source papers and 1367 high-confidence extracted claims. The evidence profile contains 4 direct clinical sources, 58 adjacent, review, or context sources, and no sources classified primarily as mechanistic or model-system evidence, with a high-density pairwise disagreement map across the evidence base. Positive study-level signals are summarized in the contextual adjacent evidence, longevity and cardiometabolic outcome classes, null signals in the contextual adjacent evidence, cardiometabolic, dosing and pharmacokinetics outcome classes, and negative signals in no dominant outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect. The conclusion is that Statin remains a bounded evidence case: the retained direct, adjacent, and context evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified broad clinical 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":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_2","claim":"This paper synthesizes evidence on Statin across 62 accepted source papers and 1367 high-confidence extracted claims.","citation_support":[],"candidate_sources":[{"study":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_3","claim":"The evidence profile contains 4 direct clinical sources, 58 adjacent, review, or context sources, and no sources classified primarily as mechanistic or model-system evidence, with a high-density pairwise disagreement map across the evidence base.","citation_support":[],"candidate_sources":[{"study":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_4","claim":"Positive study-level signals are summarized in the contextual adjacent evidence, longevity and cardiometabolic outcome classes, null signals in the contextual adjacent evidence, cardiometabolic, dosing and pharmacokinetics outcome classes, and negative signals in no dominant outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.","citation_support":[],"candidate_sources":[{"study":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_5","claim":"The conclusion is that Statin remains a bounded evidence case: the retained direct, adjacent, and context evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified broad clinical claim.","citation_support":[],"candidate_sources":[{"study":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_6","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":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_7","claim":"For Statin, what does the retained evidence show about prognostic or risk-marker associations, causal or mechanistic evidence, treatment or intervention relevance across treatment or intervention-response evidence, adjacent clinical-context evidence, biology-mechanism and molecular-context evidence, and are those outcome-class source-level signals directionally consistent enough for clinical actionability once unclear direction coding, adjacent/contextual source roles, and directness limits are considered?","citation_support":[],"candidate_sources":[{"study":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_8","claim":"Several unresolved questions thread through this evidence base and are not adequately settled by any single trial or by the corpus taken as a whole. First, the translation from mechanistic biomarker shifts to functional aging outcomes remains uncertain, and the surrogate endpoint caution that Ioannidis 2005 raises applies with particular force when short-term biochemical changes are extrapolated to long-horizon endpoints such as lifespan. Second, the tradeoffs are not symmetric across populations: in Lee 2023 dialysis patients and in Guo 2019 patients aged 80 and over, safety and adherence profiles diverge from the cardiovascular prevention populations in which statins were initially validated. Third, dose-response, duration, and population specificity, including genotype interactions noted in Asiimwe 2024a and Asiimwe 2024b, all appear to moderate any signal, suggesting that the question of whether statins can extend healthspan may not have a single answer.","citation_support":[{"source_id":"source_6","study":"Trends and outcome of statin therapy in dialysis patients with atherosclerotic cardiovascular diseases: A population-based cohort study","doi":"10.1371/journal.pone.0286670","url":"https://doi.org/10.1371/journal.pone.0286670","support_kind":"cited_as_match","cited_as":"Lee 2023","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"indirect","excerpt":"BACKGROUND: Although statins are an effective strategy for the secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in the general population, the benefits for dialysis patients are controversial. We sought to assess trends of statin use and evaluate outcomes of statin therapy in dialysis patients with different types of ASCVD. METHODS: This nationwide retrospective population-based cohort study using data from the Korean National Health Insurance Service included adult patients (aged ≥ 18 years) undergoing chronic dialysis who had an initial ASCVD event in the time period of 2013 to 2018. Annual trends of statin use according to age, sex, and ASCVD types were analyzed. The association between 1-year mortality and statin use was examined using multivariable Cox proportional hazards regression analyses. RESULTS: Among 17,242 subjects, 9,611(55.7%) patients were statin users. The overall prevalence of statin use increased from 52.9% in 2013 to 57.7% in 2018; the majority (77%) of dialysis patients were prescribed moderate-intensity statins. The proportions of low- or moderate-intensity statin use were similar, but high-intensity statin use increased from 5."},{"source_id":"source_46","study":"A prospective study of hepatic safety of statins used in very elderly patients","doi":"10.1186/s12877-019-1361-2","url":"https://doi.org/10.1186/s12877-019-1361-2","support_kind":"cited_as_match","cited_as":"Guo 2019","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"indirect","excerpt":"BACKGROUND: Statins play an important role in the care of patients with cardiovascular disease and have a good safety record in clinical practice. Hepatotoxicity is a barrier that limits the ability of primary care physicians to prescribe statins for patients with elevated liver transaminase values and/or underlying liver disease. However, limited population-based data are available on the use of statin therapy and on the hepatotoxicity of statins in very elderly patients. This prospective study evaluated the liver enzyme elevation during statin therapy in very elderly patients (≥80 years old). METHODS: Patients with hypercholesterolemia (LDL-C levels ≥3.4 and < 5.7 mmol/L), atherosclerosis, coronary heart disease (CHD), or a CHD-risk equivalent were enrolled and received once-daily statin treatment. Multivariate logistic regression models were used to study the impact of age, gender, hepatitis B infection, fatty liver disease, biliary calculus, other chronic diseases, drug kinds, alcohol abuse, statin variety, and statin dose variables. RESULTS: A total of 515 consecutive patients ranging from 80 to 98 years old were included in the analysis."}],"candidate_sources":[]},{"claim_id":"claim_9","claim":"Against this background, the present synthesis deliberately separates clinical from mechanistic inference, treats surrogate endpoint patterns as hypothesis-generating rather than confirmatory in line with the cautionary framing of Ioannidis 2005, and organizes evidence by outcome class rather than by chronology. By weighting direct randomized designs separately from observational and review-class sources, and by surfacing the within-class tensions and cross-domain contradictions that the retained corpus exposes, the analysis aims to define the boundary conditions under which the statins aging case currently holds, and to clarify which gaps an aging-focused trial would need to close. The retained statins corpus supports translation only conditionally, and the question of broader healthspan or lifespan benefit appears to remain open rather than answered.","citation_support":[],"candidate_sources":[{"study":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_10","claim":"The geroscience hypothesis holds that interventions targeting the molecular hallmarks of aging — mitochondrial dysfunction, cellular senescence, dysregulated nutrient sensing, and altered proteostasis — could compress multimorbidity in later life rather than treating each disease in isolation. Within this framework, statins are an attractive candidate because their primary pharmacological target, HMG-CoA reductase inhibition, intersects several hallmark pathways beyond low-density lipoprotein cholesterol (LDL-C) lowering, including mevalonate-derived isoprenoid signalling, mitochondrial respiratory chain assembly, and NLRP3 inflammasome priming. Regulatory bodies have so far authorised statins almost exclusively for lipid-driven cardiovascular risk reduction, leaving their broader geroscience indications — cognitive preservation, frailty attenuation, and mortality in non-cardiovascular populations — outside formal approval pathways. The implication is that any aging-related use case for statins has to be argued from off-label evidence streams and is therefore inherently indirect. This synthesis examines what the curated corpus contributes to that argument, deliberately separating directly tested RCT endpoints from observational signals that may be hypothesis-generating only.","citation_support":[],"candidate_sources":[{"study":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_11","claim":"Five methodological problems recur across the retained evidence and constrain any claim of broad aging benefit. First, surrogate-endpoint reliance is heavy: surrogate endpoints are known not to guarantee hard-outcome validity (Ioannidis 2005), and biomarker-level drops in amyloid carriers or lipid intermediates may not translate to clinical events. Second, population heterogeneity is large — older adults, dialysis patients, HIV-positive cohorts, cancer patients, and post-COVID-19 cohorts — and pooling across them obscures indication-specific effects. Third, treatment duration rarely matches the latency implied by an aging endpoint; even the 6-month Rustamzadeh 2024 protocol is short relative to dementia pathogenesis. The synthesis therefore keeps outcome-class distinctions explicit: review-class evidence should be treated as hypothesis-generating only, and direct RCT evidence remains the only basis on which substantive claims about statins in aging populations can rest.","citation_support":[{"source_id":"source_5","study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","support_kind":"cited_as_match","cited_as":"Rustamzadeh 2024","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"direct","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively)."}],"candidate_sources":[]},{"claim_id":"claim_12","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":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_13","claim":"A source was coded as direct only when it tested the topic itself against a clinically proximate outcome in the relevant population. Human evidence with an adjacent exposure, population, or outcome was coded as indirect; syntheses and secondary reviews were coded as review-level evidence and were not counted as direct sources.","citation_support":[],"candidate_sources":[{"study":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_14","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":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_15","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, muscle function, 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":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_16","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":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_17","claim":"Source directness breakdown: 4/62 retained sources directly address the stated topic and aging-relevant hard endpoints; 58/62 are adjacent, contextual, review-level, or mechanistic and are used only to bound interpretation. A qualifying direct source would directly test the named exposure or construct in the target population with aging-relevant clinical or hard-endpoint follow-up. Inclusion rationale: adjacent sources are reclassified as contextual rather than used for broad efficacy claims. Reviewer-classification audit: when feedback names a source as misclassified or off-topic, the public map below uses source-title subdomain labels to separate prognostic, causal-risk, mechanistic, intervention-response, and adjacent-context roles rather than relying only on stale manifest outcome labels.","citation_support":[],"candidate_sources":[{"study":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_18","claim":"Takada 2023: outcome=Contextual Adjacent Evidence; direction=unclear; directness=indirect; tier=B2.","citation_support":[],"candidate_sources":[{"study":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_19","claim":"Rustamzadeh 2024: outcome=Contextual Adjacent Evidence; direction=positive; directness=direct; tier=A1.","citation_support":[],"candidate_sources":[{"study":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_20","claim":"Karkeet 2022: outcome=Contextual Adjacent Evidence; direction=mixed; directness=direct; tier=A1.","citation_support":[],"candidate_sources":[{"study":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_21","claim":"Wong 2024: outcome=Contextual Adjacent Evidence; direction=unclear; directness=indirect; tier=B2.","citation_support":[],"candidate_sources":[{"study":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_22","claim":"Efficacy and Safety of Atorvastatin 2025: outcome=Dosing and Pharmacokinetics; direction=null; directness=review; tier=B2.","citation_support":[{"source_id":"source_14","study":"Efficacy and Safety of Atorvastatin and Ezetimibe (10/10mg) Fixed Dose Combination Versus Atorvastatin (20mg) Monotherapy in Bangladeshi Population","doi":null,"url":null,"support_kind":"cited_as_match","cited_as":"Efficacy and Safety of Atorvastatin 2025","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review","excerpt":"The goal of this clinical trial is to evaluate the efficacy and safety of a fixed-dose combination of atorvastatin (10 mg) and ezetimibe (10 mg) compared to atorvastatin (20 mg) monotherapy in the Bangladeshi population. Researchers will compare atorvastatin (10 mg) and ezetimibe (10 mg) to atorvastatin (20 mg) monotherapy to see if atorvastatin (10 mg) and ezetimibe (10 mg) FDC works to treat dyslipidemia."}],"candidate_sources":[]},{"claim_id":"claim_23","claim":"Turkmen 2025: outcome=Contextual Adjacent Evidence; direction=null; directness=review; tier=B2.","citation_support":[],"candidate_sources":[{"study":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_24","claim":"HMG-CoA Reductase Inhibitors 2025: outcome=Immune and Inflammation; direction=null; directness=review; tier=B2.","citation_support":[{"source_id":"source_17","study":"HMG-CoA reductase inhibitors and the attenuation of risk for disseminated intravascular coagulation in patients with sepsis: Secondary analysis finds no change in the index outcome based on reason for statin prescription","doi":"10.1182/blood-2025-1309","url":"https://doi.org/10.1182/blood-2025-1309","support_kind":"cited_as_match","cited_as":"HMG-CoA Reductase Inhibitors 2025","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review","excerpt":"<jats:title>Abstract</jats:title> <jats:sec> <jats:title/> <jats:p>'HMG-CoA reductase inhibitors and the attenuation of risk for disseminated intravascular coagulation in patients with sepsis’ published in the Journal of Thrombosis and Thrombolysis (09 November 2023 Volume 57, pages 260-268 (2024)) reports reduced odds for DIC in patients who had received high (OR 0.64; 95% CI, 0.53-0.77), moderate (OR 0.72; 95% CI, 0.61-0.84), and low intensity statins (OR 0.84; 95% CI, 0.53-1.32). While it was determined that a history of atherosclerotic heart disease (ASCVD) did not significant modify the risk for DIC (OR 0.95; 95% CI 0.84-1.07), it was not determined whether the use of statins for primary (subclinical ASCVD) or secondary (clinical ASCVD) prevention significantly modified DIC risk."}],"candidate_sources":[]},{"claim_id":"claim_25","claim":"Evolocumab Plus Ezetimibe 2020: outcome=Contextual Adjacent Evidence; direction=null; directness=review; tier=B2.","citation_support":[{"source_id":"source_19","study":"Evolocumab Plus Ezetimibe in High Risk Haemodialized Statin Intolerant Patients","doi":null,"url":null,"support_kind":"cited_as_match","cited_as":"Evolocumab Plus Ezetimibe 2020","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review","excerpt":"Patients will be randomly assigned to receive evolocumab (140 mg subcutaneous every 2 weeks + ezetimibe 10 mg per os daily) or matching placebo (subcutaneous every 2 weeks + ezetimibe 10 mg per os daily) for 24 weeks. The primary efficacy end point will be the reduction in LDL-C ≥ 20 mg/dL from baseline."}],"candidate_sources":[]},{"claim_id":"claim_26","claim":"TRIal of STatin Therapy n.d.: outcome=Deficiency Prevalence; direction=null; directness=review; tier=B2.","citation_support":[{"source_id":"source_47","study":"TRIal of STatin Therapy Effect on Androgen Status and Erectile functioN in Men","doi":null,"url":null,"support_kind":"cited_as_match","cited_as":"TRIal of STatin Therapy n.d.","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review","excerpt":"To study the effect of different intensities of statin therapy on androgen status and erectile function in men aged 40-65 years with high and very high cardiovascular risk. Group Pit (n=75) will receive pitavastatin at a starting dose of 1 mg/day."}],"candidate_sources":[]},{"claim_id":"claim_27","claim":"Multicenter Study to Evaluate 2023: outcome=Cardiometabolic; direction=null; directness=review; tier=B2.","citation_support":[],"candidate_sources":[{"study":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_28","claim":"Efficacy and Safety of Early 2026: outcome=Cardiometabolic; direction=null; directness=review; tier=B2.","citation_support":[],"candidate_sources":[{"study":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_29","claim":"Estimating Prevalence and Characteristics 2022: outcome=Cardiometabolic; direction=null; directness=review; tier=B2.","citation_support":[],"candidate_sources":[{"study":"Impact of oral statin therapy on clinical outcomes in patients with cT1 breast cancer","year":2023,"doi":"10.1186/s12885-023-10631-w","url":"https://doi.org/10.1186/s12885-023-10631-w","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":"Takada 2023","excerpt":"PURPOSE: A previous meta-analysis examining the relationship between statin use and breast cancer reported that the inhibitory effect of statins on breast cancer may be more pronounced in early-stage cases. In this study, we aimed to investigate the effects of hyperlipidemia treatment at the time of breast cancer diagnosis and to examine its correlation with metastasis to axillary lymph nodes among patients with so-called cT1 breast cancer whose primary lesion was 2 cm or less and was pathologically evaluated by sentinel lymph node biopsy or axillary lymph node dissection. We also investigated the effects of hyperlipidemic drugs on the prognosis of patients with early-stage breast cancer. METHODS: After excluding cases that did not meet the criteria, we analyzed data from 719 patients who were diagnosed with breast cancer, with a primary lesion of 2 cm or less identified by preoperative imaging, and who underwent surgery without preoperative chemotherapy. RESULTS: Regarding hyperlipidemia drugs, no correlation was found between statin use and lymph node metastasis (p = 0.226), although a correlation was found between lipophilic statin use and lymph node metastasis (p = 0.042).","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"Efficacy and safety of lipid-lowering therapies in combination with or without statin to reduce the cardiovascular risk: A systematic review of randomised controlled trials","year":2024,"doi":"10.1016/j.athplu.2024.10.001","url":"https://doi.org/10.1016/j.athplu.2024.10.001","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":"Iannuzzo 2024","excerpt":"BACKGROUND AND AIMS: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk. METHODS: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs. RESULTS: The search strategy yielded 2104 citations.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"Reno-protective effects of statins among patients with chronic kidney disease in Hong Kong: a target trial emulation","year":2026,"doi":"10.1016/j.eclinm.2026.103798","url":"https://doi.org/10.1016/j.eclinm.2026.103798","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":"Wong 2026","excerpt":"BACKGROUND: Many existing randomised controlled trials lack sufficient power to assess primary kidney outcomes. This study aimed to evaluate whether statin therapy offers a clinically meaningful reno-protective effect in patients with chronic kidney disease (CKD). METHODS: In this retrospective cohort study, electronic health records in Hong Kong were extracted to perform sequential target trial emulation. Eligible adults (aged 18+ years) with CKD who met the indication for statin initiation between Jan 1, 2008 and Dec 31, 2017 were included; those with history of estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m 2 were excluded. Participants were categorised as statin initiators or non-initiators at each calendar month during inclusion period, where statin initiators were propensity score-matched with non-initiators. Follow-up data were collected for all participants until the occurrence of outcomes, death, loss to follow-up (2 years after last records), or the end of data availability (Dec 31, 2022), whichever occurred first. The hazard ratio (HR) of all-cause mortality, eGFR deterioration (eGFR <15 mL/min/1.","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Lipid-Lowering Efficacy and Safety of a New Generic Rosuvastatin in Koreans: an 8-Week Randomized Comparative Study with a Proprietary Rosuvastatin","year":2020,"doi":"10.12997/jla.2020.9.2.283","url":"https://doi.org/10.12997/jla.2020.9.2.283","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":"Kim 2020","excerpt":"OBJECTIVE: The aim of this study was to investigate whether a new generic rosuvastatin is non-inferior to a proprietary one in terms of lipid-lowering efficacy. We also evaluated its non-lipid effects including adverse events. METHODS: One-hundred and fifty-eight patients with cardiovascular risks requiring pharmacological lipid-lowering therapy were screened. After a 4-week run-in period, 126 individuals who met the lipid criteria for drug therapy were randomly assigned to receive the new generic or proprietary rosuvastatin 10 mg daily for 8 weeks. The primary outcome variables were low-density lipoprotein-cholesterol (LDL-C) reduction and LDL-C target achievement. Hematological and biochemical parameters and adverse events were assessed. RESULTS: After 8 weeks of drug treatment, the mean percentage change in LDL-C was not different between the groups (-45.5%±19.9% and -45.1%±19.0% for generic and proprietary rosuvastatin, respectively; p =0.38). The LDL-C target achievement rate was similar between the groups (75.0% and 77.1% for generic and proprietary rosuvastatin, respectively; p =0.79). The percentage change in the other lipid profiles was not significantly different.","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer’s patients: A double-blind placebo-controlled randomized clinical trial","year":2024,"doi":"10.1016/j.ibneur.2024.07.002","url":"https://doi.org/10.1016/j.ibneur.2024.07.002","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":"direct","cited_as":"Rustamzadeh 2024","excerpt":"PURPOSE: The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated. METHODS: Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ 1-42 /Aβ 1-40 ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured. RESULTS: There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_30","claim":"Statins Against Bushfire n.d.: outcome=Contextual Adjacent Evidence; direction=unclear; directness=review; tier=B2.","citation_support":[{"source_id":"source_48","study":"Statins Against Bushfire Smoke","doi":null,"url":null,"support_kind":"cited_as_match","cited_as":"Statins Against Bushfire n.d.","population":"not extracted","endpoint":"not extracted","effect":"not extracted","directness":"review","excerpt":"The goal of this clinical trial is to test whether statins can protect the heart and brain from the biological stress and inflammatory responses caused by breathing bushfire smoke in healthy adult volunteers aged 18-64 years. Does short-term statin use (2 days) reduce bushfire smoke-induced changes in heart rate variability, blood pressure, arterial stiffness, inflammation and oxidative stress markers, and cognitive function?"}],"candidate_sources":[]}]}