{"publication_id":"f1b39b71-2cc3-43a3-ab5a-287574699c7d","content_hash":"sha256:6bd9e7045a5ba980bf33a3c0cf4304b364e0f908c67df48142f231f8359c2408","nodes":[{"id":"f1b39b71-2cc3-43a3-ab5a-287574699c7d","type":"publication","title":"Adjacent Evidence Brief: Statin — full paper"},{"id":"claim_1","type":"claim","text":"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."},{"id":"claim_2","type":"claim","text":"This paper synthesizes evidence on Statin across 62 accepted source papers and 1367 high-confidence extracted claims."},{"id":"claim_3","type":"claim","text":"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."},{"id":"claim_4","type":"claim","text":"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."},{"id":"claim_5","type":"claim","text":"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."},{"id":"claim_6","type":"claim","text":"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."},{"id":"claim_7","type":"claim","text":"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?"},{"id":"claim_8","type":"claim","text":"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."},{"id":"claim_9","type":"claim","text":"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."},{"id":"claim_10","type":"claim","text":"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."},{"id":"claim_11","type":"claim","text":"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."},{"id":"claim_12","type":"claim","text":"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."},{"id":"claim_13","type":"claim","text":"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."},{"id":"claim_14","type":"claim","text":"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."},{"id":"claim_15","type":"claim","text":"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."},{"id":"claim_16","type":"claim","text":"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."},{"id":"claim_17","type":"claim","text":"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."},{"id":"claim_18","type":"claim","text":"Takada 2023: outcome=Contextual Adjacent Evidence; direction=unclear; directness=indirect; tier=B2."},{"id":"claim_19","type":"claim","text":"Rustamzadeh 2024: outcome=Contextual Adjacent Evidence; direction=positive; directness=direct; tier=A1."},{"id":"claim_20","type":"claim","text":"Karkeet 2022: outcome=Contextual Adjacent Evidence; direction=mixed; directness=direct; tier=A1."},{"id":"claim_21","type":"claim","text":"Wong 2024: outcome=Contextual Adjacent Evidence; direction=unclear; directness=indirect; tier=B2."},{"id":"claim_22","type":"claim","text":"Efficacy and Safety of Atorvastatin 2025: outcome=Dosing and Pharmacokinetics; direction=null; directness=review; tier=B2."},{"id":"claim_23","type":"claim","text":"Turkmen 2025: outcome=Contextual Adjacent Evidence; direction=null; directness=review; tier=B2."},{"id":"claim_24","type":"claim","text":"HMG-CoA Reductase Inhibitors 2025: outcome=Immune and Inflammation; direction=null; directness=review; tier=B2."},{"id":"claim_25","type":"claim","text":"Evolocumab Plus Ezetimibe 2020: outcome=Contextual Adjacent Evidence; direction=null; directness=review; tier=B2."},{"id":"claim_26","type":"claim","text":"TRIal of STatin Therapy n.d.: outcome=Deficiency Prevalence; direction=null; directness=review; tier=B2."},{"id":"claim_27","type":"claim","text":"Multicenter Study to Evaluate 2023: outcome=Cardiometabolic; direction=null; directness=review; tier=B2."},{"id":"claim_28","type":"claim","text":"Efficacy and Safety of Early 2026: outcome=Cardiometabolic; direction=null; directness=review; tier=B2."},{"id":"claim_29","type":"claim","text":"Estimating Prevalence and Characteristics 2022: outcome=Cardiometabolic; direction=null; directness=review; tier=B2."},{"id":"claim_30","type":"claim","text":"Statins Against Bushfire n.d.: outcome=Contextual Adjacent Evidence; direction=unclear; directness=review; tier=B2."},{"id":"source_1","type":"source","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)."},{"id":"source_2","type":"source","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."},{"id":"source_3","type":"source","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."},{"id":"source_4","type":"source","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."},{"id":"source_5","type":"source","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)."},{"id":"source_6","type":"source","study":"Trends and outcome of statin therapy in dialysis patients with atherosclerotic cardiovascular diseases: A population-based cohort study","year":2023,"doi":"10.1371/journal.pone.0286670","url":"https://doi.org/10.1371/journal.pone.0286670","population":"not 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":"Lee 2023","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."},{"id":"source_7","type":"source","study":"The prognosis of lipid reprogramming with the HMG-CoA reductase inhibitor, rosuvastatin, in castrated Egyptian prostate cancer patients: Randomized trial","year":2022,"doi":"10.1371/journal.pone.0278282","url":"https://doi.org/10.1371/journal.pone.0278282","population":"not 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":"Karkeet 2022","excerpt":"AIM: The role of surgical castration and rosuvastatin treatment on lipid profile and lipid metabolism related markers was evaluated for their prognostic significance in metastatic prostate cancer (mPC) patients. METHODS: A total of 84 newly diagnosed castrated mPC patients treated with castration were recruited and divided into two groups: Group I served as control (statin non-users) while group II treated with Rosuvastatin (20 mg/day) for 6 months and served as statin users. Prostate specific antigen (PSA), epidermal growth factor receptor (EGFR), Caveolin-1 (CAV1), lipid profile (LDL, HDL, triglycerides (TG) and total cholesterol (TC)) and lipid metabolism related markers (aldoketoreductase (AKR1C4), HMG-CoA reductase (HMGCR), ATP-binding cassette transporter A1 (ABCA1), and soluble low density lipoprotein receptor related protein 1 (SLDLRP1)) were measured at baseline, after 3 and 6 months. Overall survival (OS) was analyzed by Kaplan-Meier and COX regression for prognostic significance. RESULTS: Before castration, HMG-CoA reductase was elevated in patients <65 years (P = 0.009). Bone metastasis was associated with high PSA level (P = 0.013), but low HMGCR (P = 0.004)."},{"id":"source_8","type":"source","study":"The effect of rosuvastatin alone or in combination with fenofibrate or omega-3 fatty acids on lipoprotein(a) levels in patients with mixed hyperlipidemia","year":2024,"doi":"10.5114/amsad/178441","url":"https://doi.org/10.5114/amsad/178441","population":"not 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":"Agouridis 2024","excerpt":"INTRODUCTION: Lipoprotein(a) [Lp(a)] is a strong, genetically determined, pathogenetic factor of atherosclerotic cardiovascular disease (ASCVD). The aim of this post-hoc analysis was to compare the effect of hypolipidemic treatment on Lp(a) levels of patients with mixed hyperlipidemia. MATERIAL AND METHODS: We previously randomized patients with mixed hyperlipidemia (low-density lipoprotein [LDL-C] > 160 mg/dl and triglycerides > 200 mg/dl) to rosuvastatin monotherapy 40 mg/day (R group, n = 30) or rosuvastatin 10 mg/day combined with fenofibrate 200 mg/day (RF group, n = 30) or omega-3 fatty acids 2 g/day (RΩ group, n = 30). In the present post-hoc analysis, we included only the patients whose Lp(a) levels were assessed (16, 16 and 15 in the R, RF and RΩ groups, respectively). Lipid profile and Lp(a) were measured at baseline and after 3 months of treatment. RESULTS: Significant reductions in total cholesterol, LDL-C, non-high-density lipoprotein-cholesterol (non-HDL-C) and triglyceride levels were observed in all groups. A significant increase in Lp(a) levels was noted in the R ( p = 0.017) and RF ( p = 0."},{"id":"source_9","type":"source","study":"Effects of Evolocumab Added to Moderate-Intensity Statin Therapy in Chinese Patients With Acute Coronary Syndrome: The EMSIACS Trial Study Protocol","year":2021,"doi":"10.3389/fphys.2021.750872","url":"https://doi.org/10.3389/fphys.2021.750872","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"protocol","cited_as":"Gao 2021","excerpt":"Background: Several studies have demonstrated that using a higher dose of statin can easily induce liver injury and myopathy. Low-density lipoprotein cholesterol (LDL-C) is a well-established modifiable risk factor for cardiovascular disease; however, the large majority of Chinese patients cannot meet the target level of LDL-C recommended by the Chinese expert consensus. Evolocumab has been demonstrated to reduce LDL-C by approximately 60% in many studies. Nevertheless, whether combined evolocumab and moderate-intensity statin is as effective in lowering LDL-C and decreasing incidence of MACE in Chinese patients presenting with the acute phase of acute coronary syndrome (ACS) remains unknown. Therefore, the \"Evolocumab added to Moderate-Intensity Statin therapy on LDL-C lowering and cardiovascular adverse events in patients with Acute Coronary Syndrome\" (EMSIACS) is conducted. Methods: The EMSIACS is a prospective, randomized, open-label, parallel-group, multicenter study involving analyzing the feasibility and efficacy of evolocumab added to moderate-intensity statin therapy on lowering LDL-C levels in adult Chinese patients hospitalized for acute phase ACS."},{"id":"source_10","type":"source","study":"Financial resources, access to care, and quality of care mediate racial disparities in statin usage for secondary prevention","year":2024,"doi":"10.1371/journal.pone.0311724","url":"https://doi.org/10.1371/journal.pone.0311724","population":"not 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 2024","excerpt":"BACKGROUND: There are disparities in statin therapy for the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). The role of structural racism in this disparity has not been examined. METHODS: This is a cross-sectional study of participants with ASCVD in the Medical Expenditure Panel Survey from 2014-2017. Mediation analysis is utilized to estimate the direct effect of race and indirect effect of financial resources, access to care, and quality of care on statin usage. RESULTS: The proportion of participants using statins by race/ethnicity were 58.5% for non-Hispanic Whites, 45% for Hispanics, 48.6% for Blacks, 61.6% for Asians, and 46.8% for Others. Statin usage was lower for Hispanics (OR = 0.79, 95% confidence interval [0.65-0.96]) and Blacks (OR = 0.80 [0.66-0.95]) compared to Whites. Hispanic, Black, and Other participants with the same financial resources, access to care, and quality of care as White participants did not have significantly different statin usage compared to White participants (Hispanic: OR = 0.98 [0.79-1.13]; Black (OR = 0.88 [0.76-1.06], Other: OR 0.76, 95% CI [0.56-1.15])."},{"id":"source_11","type":"source","study":"Influence of Statin Therapy on the Incidence of Cardiovascular Events, Cancer, and All-Cause Mortality in People Living With HIV: A Meta-Analysis","year":2021,"doi":"10.3389/fmed.2021.769740","url":"https://doi.org/10.3389/fmed.2021.769740","population":"not 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":"Li 2021","excerpt":"Background: Possible influences of statin therapy on the risk of cardiovascular events, cancer, and all-cause mortality in people living with HIV (PLWH) remain unclear. We performed a meta-analysis to systematically evaluate the efficacy of statin in PLWH. Methods: Relevant cohort studies were retrieved via a search of the Medline, the Embase, and the Web of Science databases until June 14, 2021. The data were combined with a random-effects model by incorporating the between-study heterogeneity. Results: A total of 12 multivariate cohort studies with 162,252 participants were eligible for the meta-analysis and 36,253 (22.3%) of them were statin users. Pooled results showed that statin use was independently related to a reduced mortality risk in PLWH [adjusted risk ratio (RR): 0.56, 95% CI: 0.44 to 0.72, p < 0.001, I 2 = 41%]. In addition, results of the meta-analysis showed that statin use was not significantly associated with a reduced risk of cardiovascular events in PLWH compared to the statin non-users (RR: 1.14, 95% CI: 0.80 to 1.63, p = 0.48, I 2 = 42%). However, statin use was significantly related to a reduced risk of cancer in PLWH (RR: 0.73, 95% CI: 0.58 to 0.93, p = 0."},{"id":"source_12","type":"source","study":"Candesartan, Metoprolol and Rosuvastatin Associated to Lower 30-Days Mortality in Adult COVID-19 Patients – A Register Study in Finland before COVID-19 Vaccines","year":2026,"doi":"10.1177/21501319261453019","url":"https://doi.org/10.1177/21501319261453019","population":"not 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":"Hyvarinen 2026","excerpt":"Elderly people with chronic diseases are at risk for having severe COVID-19 disease. We were interested whether the drugs prescribed for the chronic diseases are associated with lower mortality in COVID-19 patients.We used Finnish national registry data for analysis of potential associations of 73 prescription drugs to mortality among 6082 adult COVID-19 patients between 1.1.2020 and 30.6.2020, before COVID-19 vaccinations were available. Adjusted odds ratios (aORs) with 95 percent confidence intervals (95% CIs) for different medications are presented.The use of three cardiovascular drugs was associated with lower 30 days all-cause mortality rate: candesartan (aOR 0.34, 95% CI 0.16-0.72, p=0.005), metoprolol (aOR 0.37, 95% CI 0.16-0.88, p=0.024) and rosuvastatin (aOR 0.44, 95% CI 0.21-0.94, p=0.034).In conclusion, COVID-19 patients who used cardiovascular drugs candesartan, metoprolol or rosuvastatin have lower 30 days all-cause mortality than other COVID-19 patients."},{"id":"source_13","type":"source","study":"Abstract 12870: Absence of LDL Measurement in Secondary Prevention is Associated With Increased Subsequent Major Adverse Clinical Event (MACE) That is Only Partially Mitigated by Statin Use","year":2022,"doi":"10.1161/circ.146.suppl_1.12870","url":"https://doi.org/10.1161/circ.146.suppl_1.12870","population":"not 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":"MACE 2022","excerpt":"We therefore set out to determine in a large healthcare system whether measurement of LDL-C after an ASCVD event was associated with a difference in MACE during follow-up and whether differences in outcomes could be attributed to differences in statin use. </jats:p> <jats:p> <jats:bold>Methods:</jats:bold> The Intermountain Enterprise Data Warehouse was searched to identify all adults with a first encounter for ASCVD-including coronary artery disease (CAD), cerebrovascular disease (CVD), and peripheral arterial disease (PAD)-between January 1, 1995 and December 31, 2016 who survived the index event and were followed for ≥3 years or until death. </jats:p> <jats:p> <jats:bold>Results:</jats:bold> Patients (N=68,411) had an average age of 66±14 years; 65% were men; 70.3%, 21.0%, and 8.6% entered with CAD, CVD, and PAD, respectively. A statin was prescribed to 52% of patients during follow-u"},{"id":"source_14","type":"source","study":"Efficacy and Safety of Atorvastatin and Ezetimibe (10/10mg) Fixed Dose Combination Versus Atorvastatin (20mg) Monotherapy in Bangladeshi Population","year":2025,"doi":null,"url":null,"population":"not 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":"Efficacy and Safety of Atorvastatin 2025","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."},{"id":"source_15","type":"source","study":"APOEGenotype and Statin Response: Evidence from Electronic Health Records in the UK Biobank and All of Us Research Program","year":2024,"doi":"10.1101/2024.12.13.24318985","url":"https://doi.org/10.1101/2024.12.13.24318985","population":"not 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":"Asiimwe 2024a","excerpt":"Results After Bonferroni correction, significant changes in HDLC and triglyceride levels were observed in both cohorts ( P < 0.01) following statin initiation. For all-cause mortality, significant associations were found in the UKB cohort, with ε3ε4 (HR: 1.08, 95% CI: 1.01-1.15) and ε4ε4 (HR: 1.54, 1.33-1.78) carriers showing higher risk compared to the reference ε3ε3 genotype."},{"id":"source_16","type":"source","study":"Understanding the causes and consequences of low statin adherence: evidence from UK Biobank primary care data","year":2025,"doi":"10.1101/2025.01.23.25321011","url":"https://doi.org/10.1101/2025.01.23.25321011","population":"not 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":"Turkmen 2025","excerpt":"Methods We analysed 76,000 UK Biobank participants prescribed atorvastatin or simvastatin in primary care: 41,000 had LDL-c measurements before statin initiation (median=16 days prior, IQR=28) and within a year of starting treatment (median=89 days, IQR=125). LDL-c reduction was greater in those with high adherence versus lower adherence (38% reduction when PDC>95% [high] vs."},{"id":"source_17","type":"source","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","year":2025,"doi":"10.1182/blood-2025-1309","url":"https://doi.org/10.1182/blood-2025-1309","population":"not 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":"HMG-CoA Reductase Inhibitors 2025","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."},{"id":"source_18","type":"source","study":"Effects of Statin for Elderly Patients With Atherosclerotic Cardiovascular Disease","year":2023,"doi":null,"url":null,"population":"not 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":"Effects of Statin for Elderly 2023","excerpt":"Therefore, US and European recommendations recommend that established ASCVD patients (coronary artery disease, cerebrovascular disease, peripheral vascular disease) use high-dose statins to lower LDL cholesterol levels by at least 50%. These muscle side effects are dose-dependent and are common at high doses, and the incidence is known to increase in the elderly over 70 years of age."},{"id":"source_19","type":"source","study":"Evolocumab Plus Ezetimibe in High Risk Haemodialized Statin Intolerant Patients","year":2020,"doi":null,"url":null,"population":"not 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":"Evolocumab Plus Ezetimibe 2020","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."},{"id":"source_20","type":"source","study":"Efficacy and Safety of Early Combined Therapy With PCSK9 Inhibitors and Statins in Acute Ischemic Stroke","year":2026,"doi":null,"url":null,"population":"not 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":"Efficacy and Safety of Early 2026","excerpt":"Patients will be centrally randomized in a 1:1 ratio into two groups: Experimental Group: A single subcutaneous injection of 420 mg evolocumab upon admission, combined with standard doses of atorvastatin 20 mg or rosuvastatin 10 mg, along with other standard guideline-based medical treatments. Control Group: Standard doses of atorvastatin 20 mg or rosuvastatin 10 mg, with the remainder of treatment based on current guidelines."},{"id":"source_21","type":"source","study":"A Multicenter Study to Evaluate the Effect of High Dose Rosuvastatin Versus Rosuvastatin and Ezetimibe in Stroke","year":2023,"doi":null,"url":null,"population":"not 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":"Multicenter Study to Evaluate 2023","excerpt":"Statin therapy is recommended even if it is less than 100 mg/dL. The 2016 ESC/EAS and 2017 AACE guidelines include ischemic stroke and transient cerebral ischemic attacks caused by atherosclerosis in ASCVD, classifying them as ultra-high-risk groups, and recommending LDL cholesterol of less than 70 mg/dL as a treatment goal."},{"id":"source_22","type":"source","study":"Estimating prevalence and characteristics of statin intolerance among high and very high cardiovascular risk patients in Germany between 2017–2020","year":2022,"doi":null,"url":null,"population":"not 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":"Estimating Prevalence and Characteristics 2022","excerpt":"After deploying machine learning, the SI identification improved by ∼27% in absolute SI and by ∼57% in partial SI patients, resulting in a maximum estimate of 12.5% SI with high/moderate confidence and further 11.8% with low confidence (absolute SI 15.8%, partial SI 8.5%). Atorvastatin 40mg was the most frequently down-titrated statin, while simvastatin to atorvastatin was the most predominant class switch in SI patients."},{"id":"source_23","type":"source","study":"Relationship Between Insulin Resistance and Statin Induced Type 2 Diabetes, and Integrative Personal Omics Profiling","year":2020,"doi":null,"url":null,"population":"not 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":"Relationship between Insulin Resistance 2020","excerpt":"The goals of this study are to: 1. determine the effect of high-intensity atorvastatin (40 mg/day) for \\~ 10 weeks on insulin sensitivity and insulin secretion (defined with gold standard methods) (PRIMARY OUTCOMES) as well as other glycemic traits (SECONDARY OUTCOMES); 2. compare a number of cardio-metabolic characteristics (e.g. weight, lipids) before, during, and after administration of atorvastatin; 3. determine if significant deterioration of insulin action and/or secretion following statin treatment will be confined to those with baseline insulin resistance (PRE-SPECIFIED SUBGROUP ANALYSES); 4. perform Personal Omics Profiling (iPOP) 6,7 before and after taking atorvastatin to examine treatment-associated changes in all baseline variables and to analyze not only previously-known drug efficacy but also untargeted drug efficacy (EXPLORATORY ANALYSES). General approach: This will be a"},{"id":"source_24","type":"source","study":"Effect of Simvastatin Withdrawal on Ocular Endothelial Function","year":2020,"doi":null,"url":null,"population":"not 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":"Effect of Simvastatin Withdrawal 2020","excerpt":"In a recently published study, discontinuation of statin therapy in patients after acute myocardial infarction was associated with a higher all-cause mortality (hazard ratio 3,45) and a higher cardiac mortality (hazard ratio 4,65). For this purpose 20 healthy subjects will be treated with 40 mg/day of simvastatin for a period of 4 weeks."},{"id":"source_25","type":"source","study":"Statin TReatment for COVID-19 to Optimise NeuroloGical recovERy","year":2025,"doi":null,"url":null,"population":"not 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":"Statin TReatment for COVID 2025","excerpt":"STRONGER is an international, investigator initiated and conducted, pragmatic clinical trial to determine whether 40mg atorvastatin daily can improve neurocognitive function in adults with long COVID neurological symptoms. The objective is to determine effectiveness of treatment with 40mg atorvastatin over 12 months on attenuating cognitive decline and neuroinflammatory biomarkers in adults with long COVID neurological symptoms."},{"id":"source_26","type":"source","study":"Envafolimab With Chemotherapy and Simvastatin in Advanced Biliary Tract Cancer","year":2026,"doi":null,"url":null,"population":"not 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":"Envafolimab with Chemotherapy and Simvastatin 2026","excerpt":"Receive Envafolimab (IV infusion) + gemcitabine/cisplatin (chemotherapy) + simvastatin (oral pill) every 3 weeks for up to 8 cycles (\\~6 months). After 8 cycles, continue with Envafolimab + simvastatin alone every 4 weeks until cancer worsens or side effects become too severe."},{"id":"source_27","type":"source","study":"Randomized Comparison of Efficacy and Safety of High-intensity Rosuvastatin/Ezetimibe Combination Versus Treat-to-target Rosuvastatin Monotherapy for Patients With Peripheral Artery or Polyvascular Disease (CARE-PVD Trial)","year":2026,"doi":null,"url":null,"population":"not 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":"Randomized Comparison of Efficacy 2026","excerpt":"Thus, the purpose of the CARE-PVD study is to investigate whether the combination therapy of high intensity rosuvastatin 20 mg plus ezetimibe 10 mg can improve cardiovascular outcomes in patient with peripheral artery disease or polyvascular artery disease in comparison with rosuvastatin treat-to-target (LDL cholesterol \\<70 mg/dL) monotherapy."},{"id":"source_28","type":"source","study":"STATIC - Statin Termination in Cancer","year":2026,"doi":null,"url":null,"population":"not 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":"STATIC Statin Termination 2026","excerpt":"At start of the study statins are deprescribed and the patients are followed for 12 weeks. A control group (n=40) comprising patients with advanced cancer and no ongoing statin treatment, are included from the same specialized palliative care units."},{"id":"source_29","type":"source","study":"APOE Genotype and Statin Response: Evidence from the UK Biobank Baseline Assessment and Linked Mortality Data","year":2024,"doi":"10.1101/2024.12.13.24318982","url":"https://doi.org/10.1101/2024.12.13.24318982","population":"not 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":"Asiimwe 2024b","excerpt":"Results Significant interactions between APOE genotype and statin use were observed for most lipid biomarkers at the Bonferroni-adjusted threshold ( P < 0.007), including Apolipoprotein A ( P = 0.0065), Apolipoprotein B ( P < 2.00e-16), LDLC, Total Cholesterol, and Triglycerides (all P < 2.00e-16), and HDLC ( P = 0.0001)."},{"id":"source_30","type":"source","study":"Changes in Plaque Characteristics After Short-term Statin Therapy as Assessed With Coronary CT","year":2026,"doi":null,"url":null,"population":"not 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":"Changes in Plaque Characteristics 2026","excerpt":"INTENSE Trial is a prospective, double-blind, randomized, placebo-controlled, single-center study with two arms (40 mg intensified statin therapy vs matching placebo for rosuvastatin) among statin-naive patients referred to coronary CT angiography due to stable chest pain, followed for 24 months by using a photon-counting detector CT (PCD-CT)."},{"id":"source_31","type":"source","study":"Evaluate the Efficacy and Safety of Atorvastatin Combined With Temozolomide in the Treatment of Glioblastoma","year":2026,"doi":null,"url":null,"population":"not 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":"Evaluate the Efficacy and Safety 2026","excerpt":"Glioblastoma (GBM) is the primary intracranial malignant tumor with the highest morbidity and mortality, and the 5-year survival rate is less than 10%. At present, the clinical treatment strategy of maximum surgical resection combined with concurrent chemo- and radio-therapy and TTF treatment is still not satisfactory, and the median survival time of GBM patients is only 14.4 months."},{"id":"source_32","type":"source","study":"Major Adverse Cardiovascular Events (MACE) in Rheumatoid Arthritis Patient With Moderate to Severe Disease Activity Treated With Tofacitinib and Statins vs TNF Inhibitors: TOFSTAT CLINICAL TRIAL","year":2026,"doi":null,"url":null,"population":"not 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":"MACE 2026","excerpt":"PRIMARY OBJECTIVE * To determine the incidence of MACE in Rheumatoid Arthritis patients with moderate to high disease activity and with one or more cardiovascular disease risks, which are non-responsive to standard conventional DMARDs (cDMARDs) treatment and are prescribed Tofacitinib 5 mg twice daily along with statin 20 mg daily versus TNF Inhibitors. * The study aim to compare MACE in RA patients treated with tofacitinib and statin versus TNF inhibitors."},{"id":"source_33","type":"source","study":"Effects of statin treatment on primary and hospital care use: a microsimulation model","year":2025,"doi":"10.1101/2025.09.30.25337016","url":"https://doi.org/10.1101/2025.09.30.25337016","population":"not 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":"Zhou 2025","excerpt":"These models were integrated into a validated cardiovascular disease (CVD) microsimulation policy model to assess statin treatment effects on healthcare use in population categories by age (40-60 years and 60-70 years) and prior CVD history."},{"id":"source_34","type":"source","study":"Atorvastatin for Reduction of 28-day Mortality in COVID-19: RCT","year":2021,"doi":null,"url":null,"population":"not 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":"Atorvastatin for Reduction of Day 2021","excerpt":"This randomized placebo-controlled double-blinded clinical trial aims to test the efficacy of administering atorvastatin 40 mg to hospitalized COVID-19 patients for 28 days on the all-cause 28-day mortality."},{"id":"source_35","type":"source","study":"Statin Monotherapy or Statins in Combination With Ezetimibe in Patients for Prevention of CVD","year":2021,"doi":null,"url":null,"population":"not 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":"Statin Monotherapy or Statins 2021","excerpt":"The study will include patients receiving lipid-lowering therapy in both primary and secondary prevention of CVD who have received therapy of interest for ≥ 3 months in the 2 years preceding the signing of informed consent, i.e. statins as monotherapy or in combination with ezetimibe in a stable mode (without dose adjustment and/or statin replacement)."},{"id":"source_36","type":"source","study":"The Effects of Rosuvastatin on Running Training Adaptation and Safety","year":2026,"doi":null,"url":null,"population":"not 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":"Effects of Rosuvastatin on Running 2026","excerpt":"After informed consent and baseline cardiopulmonary exercise testing (CPET), participants will be randomized to rosuvastatin 10 mg daily or no statin therapy for three months."},{"id":"source_37","type":"source","study":"Ursodeoxycholic Acid Attenuates Statin-Induced Impaired Glucose Tolerance","year":2026,"doi":null,"url":null,"population":"not 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":"Ursodeoxycholic Acid Attenuates 2026","excerpt":"Participants will: * Take Atorvastatin combined with UDCA or a placebo daily for 6 months * Have follow-up visits on day 40, day 110, and day 180 Have their examination indicators recorded."},{"id":"source_38","type":"source","study":"A randomised clinical trial of STAtin therapy for Reducing Events in the Elderly (STAREE): Statistical analysis plan","year":2025,"doi":"10.1101/2025.02.24.25321974","url":"https://doi.org/10.1101/2025.02.24.25321974","population":"not 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":"Wolfe 2025","excerpt":"ABSTRACT The STAREE randomised controlled trial of 9971 community-dwelling older adults without cardiovascular disease, diabetes or dementia is designed to compare daily 40mg atorvastatin to placebo."},{"id":"source_39","type":"source","study":"Clinical validation of a statin-benefit polygenic score using real-world cohorts of primary prevention participants","year":2025,"doi":"10.1101/2025.10.09.25337698","url":"https://doi.org/10.1101/2025.10.09.25337698","population":"not 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":"Haldar 2025","excerpt":"Results Across all cohorts, statin use was more strongly associated with reduced risk of major adverse cardiovascular events among participants with no myocardial infarction at index in the highest versus lowest polygenic risk score group for the PRS2022 (interaction beta 0.19, standard error 0.07, interaction P =2.3E-3) and metaGRS (interaction beta 0.14, standard error 0.07, interaction P =.02) scores."},{"id":"source_40","type":"source","study":"Statin Reminders for Improving Prescribing in Primary Care","year":2024,"doi":null,"url":null,"population":"not 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":"Statin Reminders for Improving 2024","excerpt":"Statins reduce cardiovascular events and mortality, but only 30% of eligible primary care patients nationally are on statins."},{"id":"source_41","type":"source","study":"Statin Monotherapy for Treatment of Endocrine Metabolic Disease Risk","year":2022,"doi":null,"url":null,"population":"not 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":"Statin Monotherapy for Treatment 2022","excerpt":"Treatment: Subjects will be prescribed Rosuvastatin 10 mg daily or a sugar pill."},{"id":"source_42","type":"source","study":"Effects of Atorvastatin in Graves' Orbitopathy (GO)","year":2021,"doi":null,"url":null,"population":"not 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":"Effects of Atorvastatin in Graves' 2021","excerpt":"In a large retrospective study conducted in more than 8,000 individuals with GD it was observed that treatment with 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitors, better known as statins, is associated with a \\~40% reduced risk of developing GO in GD patients."},{"id":"source_43","type":"source","study":"Intermediate-dose vs Standard Prophylactic Anticoagulation and Statin vs Placebo in ICU Patients With COVID-19","year":2021,"doi":null,"url":null,"population":"not 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":"Intermediate-dose vs Standard Prophylactic 2021","excerpt":"The second randomization will be double-blind assignment of the included patients to atorvastatin 20mg daily versus matching placebo."},{"id":"source_44","type":"source","study":"Pravastatin to Prevent Preeclampsia","year":2021,"doi":null,"url":null,"population":"not 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":"Pravastatin to Prevent Preeclampsia 2021","excerpt":"Women with a prior history of preeclampsia with preterm delivery less than 34 weeks will be randomized to pravastatin or placebo daily until delivery."},{"id":"source_45","type":"source","study":"StAtins for Venous Event Reduction in Patients With Venous Thromboembolism Pilot Study","year":2020,"doi":null,"url":null,"population":"not 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":"StAtins for Venous Event 2020","excerpt":"Eligible consenting patients who developed acute, symptomatic, and objectively confirmed proximal leg deep vein thrombosis (DVT) and/or PE will be randomized and equally allocated to 2 trial arms, either the treatment group (rosuvastatin tablet (20 mg/day) or the control group (usual care)."},{"id":"source_46","type":"source","study":"A prospective study of hepatic safety of statins used in very elderly patients","year":2019,"doi":"10.1186/s12877-019-1361-2","url":"https://doi.org/10.1186/s12877-019-1361-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"indirect","cited_as":"Guo 2019","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."},{"id":"source_47","type":"source","study":"TRIal of STatin Therapy Effect on Androgen Status and Erectile functioN in Men","year":null,"doi":null,"url":null,"population":"not 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":"TRIal of STatin Therapy n.d.","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."},{"id":"source_48","type":"source","study":"Statins Against Bushfire Smoke","year":null,"doi":null,"url":null,"population":"not 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":"Statins Against Bushfire n.d.","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?"},{"id":"source_49","type":"source","study":"Statin Therapy With Atorvastatin in Surgical Aortic Valve Replacement","year":null,"doi":null,"url":null,"population":"not 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":"Statin Therapy with Atorvastatin n.d.","excerpt":"Patients will be randomized to Atorvastatin 80mg or placebo 7 to 14 days preoperative until 30 days postoperative - a total of 37 to 44 days of treatment. The randomized studie will address the following hypotheses in patients undergoing open heart operation with solitary aortic valve replacement with a bioprosthetic valve that 1\\) 7 to 14 days preoperative and until 30 days postoperative treatment with Atorvastatin 80 mg daily reduces the incidence of POAF in statin-naïve patients."},{"id":"source_50","type":"source","study":"A 12-Week, Phase 2 Study of Gemcabene in Hypercholesterolemia Patients on Stable Moderate and High-Intensity Statins","year":2017,"doi":null,"url":null,"population":"not 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":"Week Phase Study 2017","excerpt":"The purpose of this study was to assess the efficacy, safety, and tolerability of multiple doses of gemcabene 600 mg QD compared to placebo in patients with hypercholesterolemia not adequately controlled on high-intensity or moderate-intensity stable statin therapy. Patients with HeFH, ASCVD, or otherwise uncontrolled, may be included with baseline LDL-C value ≥ 100 mg/dL."},{"id":"source_51","type":"source","study":"MUscle Side-Effects of Atorvastatin in Coronary Patients","year":2019,"doi":null,"url":null,"population":"not 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":"MUscle Side-Effects of Atorvastatin 2019","excerpt":"Patients will be randomized to 7-weeks treatment with atorvastatin 40 mg/day in the first period and matched placebo in the second 7-weeks period, or placebo in the first period and atorvastatin in the second period. A control group (n=40) without muscle symptoms will have 7 weeks open treatment with atorvastatin 40 mg/day."},{"id":"source_52","type":"source","study":"Effects of Simvastatin and Micronized Trans-resveratrol Treatment on Polycystic Ovary Syndrome (PCOS) Patients","year":2017,"doi":null,"url":null,"population":"not 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":"PCOS 2017","excerpt":"Methods: A randomized (1:1) double-blind, placebo-controlled trial will evaluate the effects of administering 20 mg of simvastatin daily and 500 mg of resveratrol daily, or administering 20 mg simvastatin and the placebo to women with PCOS at an academic hospital."},{"id":"source_53","type":"source","study":"Evaluation of Rosuvastatin Effect as Adjuvant Therapy to Methotrexate on Lipid Profile and the Possibility of its Cardioprotective Effect in Iraqi Patients with Active Rheumatoid Arthritis","year":2017,"doi":null,"url":null,"population":"not 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":"Evaluation of Rosuvastatin Effect 2017","excerpt":"A double blinded placebo controlled clinical trial with 8 weeks follow up periods at which 40 patients with active RA using MTX were randomized into 2 groups to receive either rosuvastatin 10mg or placebo as adjuvant therapy to MTX. At the end of the study rosuvastatin significantly reduced ESR, TC and LDLc after 8 weeks of treatment."},{"id":"source_54","type":"source","study":"Simvastatin Addition for Patients With Recent-onset Schizophrenia","year":2019,"doi":null,"url":null,"population":"not 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":"Simvastatin Addition for Patients 2019","excerpt":"Hypotheses: Daily treatment with 40mg simvastatin in addition to antipsychotic treatment reduces psychotic symptoms, improves cognition, attenuates brain volume loss, and decreases the risk for metabolic syndrome as well as for movement disorders, when compared to placebo. Intervention: Patients will be randomized 1:1 to either 40 mg simvastatin or placebo daily, in the form of identical tablets."},{"id":"source_55","type":"source","study":"Effect of Pravastatin in the Subjects With Prediabetes or Early Diabetes","year":2017,"doi":null,"url":null,"population":"not 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":"Effect of Pravastatin in the Subjects 2017","excerpt":"In the West of Scotland Coronary Prevention Study, pravastatin therapy reduced the hazard of becoming diabetic by 30%. In this clinical trial, the investigators are aiming to evaluate the effect of pravastatin on insulin resistance, insulin secretion, glycemic control, and adiponectin level in participants with prediabetes or early diabetes by assigning them in a 24 weeks of pravastatin therapy group or in a placebo group."},{"id":"source_56","type":"source","study":"Rosuvastatin for Prevention of Anthracycline-induced Cardiac Dysfunction in Breast Cancer Patients","year":null,"doi":null,"url":null,"population":"not 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":"Rosuvastatin for Prevention of Anthracycline-induced n.d.","excerpt":"This study, called \"ROSUBREAST\", is a multicenter, double-blind, randomized clinical trial evaluating whether rosuvastatin (20 mg daily) can protect the heart in women with breast cancer receiving anthracycline-based chemotherapy. A total of 400 participants will be randomly assigned to receive either rosuvastatin or placebo for 12 months."},{"id":"source_57","type":"source","study":"Does Rosuvastatin Delay Progression of Atherosclerosis in HIV","year":2018,"doi":null,"url":null,"population":"not 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":"Does Rosuvastatin Delay 2018","excerpt":"Placebo=0.0062 (±0.0039); Rosuvastatin=0.004 (±0.0036). p=0.684"},{"id":"source_58","type":"source","study":"Pravastatin Intervention to Delay Hepatocellular Carcinoma Recurrence","year":2018,"doi":null,"url":null,"population":"not 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":"Pravastatin Intervention to Delay 2018","excerpt":"Out of every 100 patients with liver cancer, only 18 will survive 5 years or more."},{"id":"source_59","type":"source","study":"Atorvastatin Pretreatment in Cerebrovascular Events (APICES) After Flow Diverter Implantation","year":null,"doi":null,"url":null,"population":"not 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":"APICES n.d.","excerpt":"APICES trial is an investigator-initiated, multicenter, multicenter, randomized, double-blind, placebo-controlled clinical trial that plans to enroll 396 patients with a 1-year follow-up, including a neurovascular imaging examination \\[digital subtraction angiography (DSA), CT angiography (CTA) or magnetic resonance angiography (MRA)\\] at 6 months after index treatment."},{"id":"source_60","type":"source","study":"Carvedilol + Simvastatin vs. Carvedilol Alone for Cirrhosis and Cirrhotic Cardiomyopathy and Impact on Hepatic Decompensation and Survival","year":null,"doi":null,"url":null,"population":"not 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":"Carvedilol Simvastatin vs Carvedilol n.d.","excerpt":"CCM, present in 30-70% of patients, is characterized by structural and functional abnormalities in the heart, and is associated with progression of cirrhosis, impaired quality of life and poor survival."},{"id":"source_61","type":"source","study":"Comparison of Pitavastatin Plus Ezetimibe Versus High-Intensity Statin Therapy on Risk of New-Onset Diabetes Mellitus","year":null,"doi":null,"url":null,"population":"not 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":"Comparison of Pitavastatin Plus n.d.","excerpt":"The study evaluates pitavastatin plus ezetimibe combination therapy versus high-intensity statin monotherapy (rosuvastatin 20 mg)."},{"id":"source_62","type":"source","study":"Moderate-intensity Statin vs. Individualized LDL-C Target-based Therapy in Older Adults With Type 2 Diabetes (iTARGET-Elderly Study)","year":null,"doi":null,"url":null,"population":"not 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":"Moderate-intensity Statin vs Individualized n.d.","excerpt":"While the benefits of intensive LDL-C lowering are well-established for secondary prevention, evidence remains insufficient for primary prevention in the elderly-specifically for individuals aged 70 years or older with type 2 diabetes who have no prior history of atherosclerotic cardiovascular 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