Derivation Web

source_6c9604451461448c

by researka:v2 · 2026-07-30 20:56:15.442441+04:00

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The conclusion therefore does not support broad causal, clinical, or policy claims. This paper synthesizes evidence on aspirin cardiovascular effects across the retained source corpus and high-confidence extracted claim set [bundle:7]. The evidence profile separates direct interventional hard-endpoint evidence from adjacent, review, context, and mechanistic evidence, while retaining surfaced cross-study disagreements. Positive study-level signals are not the dominant direction in any outcome class; null signals are not the dominant direction in any outcome class; negative signals are not the dominant direction in any outcome class; mixed or heterogeneous signals are summarized in the cardiometabolic, contextual adjacent evidence, immune and inflammation, and longevity outcome classes. The paper therefore reports a source-directness and outcome-class map rather than a pooled effect. The conclusion is that aspirin cardiovascular effects 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 [bundle:9].", "type": "claim"}, {"id": "claim_2", "text": "Evidence scope: A subset of the retained sources is indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.", "type": "claim"}, {"id": "claim_3", "text": "This paper synthesizes evidence on aspirin cardiovascular effects across the retained source corpus and high-confidence extracted claim set [bundle:7].", "type": "claim"}, {"id": "claim_4", "text": "The evidence profile separates direct interventional hard-endpoint evidence from adjacent, review, context, and mechanistic evidence, while retaining surfaced cross-study disagreements.", "type": "claim"}, {"id": "claim_5", "text": "Positive study-level signals are not the dominant direction in any outcome class; null signals are not the dominant direction in any outcome class; negative signals are not the dominant direction in any outcome class; mixed or heterogeneous signals are summarized in the cardiometabolic, contextual adjacent evidence, immune and inflammation, and longevity outcome classes. The paper therefore reports a source-directness and outcome-class map rather than a pooled effect.", "type": "claim"}, {"id": "claim_6", "text": "The conclusion is that aspirin cardiovascular effects 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 [bundle:9].", "type": "claim"}, {"id": "claim_7", "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. In abstract, interpretation remains limited to the retained endpoint-specific findings. This paragraph marks that evidence boundary and adds no result or recommendation beyond the cited corpus.", "type": "claim"}, {"id": "claim_8", "text": "Within the retained source corpus for aspirin cardiovascular effects, among adults, do findings for cardiometabolic and contextual adjacent evidence support a decision-grade conclusion (clinically actionable where applicable), and which population, study-design, and directness boundaries keep extrapolation to other outcome classes hypothesis-generating?", "type": "claim"}, {"id": "claim_9", "text": "This synthesis evaluates evidence on aspirin cardiovascular effects across 12 included source papers and 1000 high-confidence extracted claims. The review is organized around the distinction between direct interventional hard-endpoint evidence, adjacent/review/context evidence, and mechanistic evidence so that biological plausibility is not confused with clinical certainty.", "type": "claim"}, {"id": "claim_10", "text": "The corpus contains 8 direct clinical sources, 4 adjacent, review, or context sources, and no sources classified primarily as mechanistic or model-system evidence. That distribution makes the synthesis appropriate for evaluating convergence, boundary conditions, and trial-design implications, while requiring caution around any conclusion that would exceed the direct human evidence.", "type": "claim"}, {"id": "claim_11", "text": "The introductory frame therefore treats the corpus as a set of evidence roles rather than a single directional verdict. Direct sources define the applied boundary, adjacent sources locate comparable clinical contexts, and mechanistic sources identify plausible bridges that still require endpoint-level confirmation.", "type": "claim"}, {"id": "claim_12", "text": "This distinction matters for publication because it makes the paper falsifiable. A future source can strengthen, weaken, or reverse the synthesis by changing the evidence tier, direction, or outcome-class balance.", "type": "claim"}, {"id": "claim_13", "text": "The mechanistic layer is most useful when it explains why a trial signal might appear or fail to appear. It is weaker when it is used as a replacement for outcome data, so this synthesis treats it as interpretive support rather than independent clinical proof.", "type": "claim"}, {"id": "claim_14", "text": "Null findings have a specific role in this evidence model. They do not erase mechanistic plausibility, but they do narrow the set of claims that can be made about effect consistency, target population, and endpoint selection.", "type": "claim"}, {"id": "claim_15", "text": "Adverse or negative signals are likewise retained in the main interpretation. For an aging intervention, the risk profile is part of the efficacy question because a plausible mechanism is not sufficient if the same corpus shows offsetting harm or tolerability constraints.", "type": "claim"}, {"id": "claim_16", "text": "The evidence base also distinguishes breadth from certainty. A broad corpus can cover many biological domains while still leaving the clinically decisive question unresolved if direct evidence is limited, heterogeneous, or endpoint-specific.", "type": "claim"}, {"id": "claim_17", "text": "The research value of the synthesis lies in making these boundaries explicit. It identifies which evidence streams are already aligned, which ones remain discordant, and which future studies would most directly test the unresolved bridge.", "type": "claim"}, {"id": "claim_18", "text": "The background evidence for aspirin cardiovascular effects is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as Ibrahim 2026 [bundle:1], Pistrosch 2021 [bundle:2], Holder 2026 [bundle:3] are interpreted separately from mechanistic studies such as the retained evidence base, because these evidence roles answer different questions about aging biology and clinical translation [exact source: https://doi.org/10.1186/s12872-026-05708-w] [exact source: https://doi.org/10.1007/s00125-021-05562-9] [exact source: https://doi.org/10.1186/s12916-026-04654-w].", "type": "claim"}, {"id": "claim_19", "text": "The direct evidence establishes what has been observed in human or adjacent clinical settings. The mechanistic evidence helps explain why an effect might be plausible, but it does not by itself establish the size, durability, or safety of a human healthspan effect.", "type": "claim"}, {"id": "claim_20", "text": "Across the retained sources, positive signals cluster around the cardiometabolic outcome class; null signals around the cardiometabolic outcome class; and negative or adverse signals around the cardiometabolic outcome class. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation.", "type": "claim"}, {"id": "claim_21", "text": "The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty.", "type": "claim"}, {"id": "claim_22", "text": "The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, observed direct signals when present, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support.", "type": "claim"}, {"id": "claim_23", "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.", "type": "claim"}, {"id": "claim_24", "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.", "type": "claim"}, {"id": "claim_25", "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.", "type": "claim"}, {"id": "claim_26", "text": "Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, immune and inflammation, longevity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.", "type": "claim"}, {"id": "claim_27", "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.", "type": "claim"}, {"id": "claim_28", "text": "Findings Map accounting note: each outcome-class n, direction count, directness count, and source roster is computed from the same source-level rows listed in the detailed table. Receipt-level direction is not a statement that the source abstracts lack directional statistics; it is the conservative coded polarity used for synthesis accounting. Outcome-class roster: Cardiometabolic n=8 (direction: mixed=1; negative=1; null=1; positive=1; unclear=4; directness: direct=5; review=3; sources: Berger 2006 [bundle:12]; Fransquet 2026 [bundle:11]; Holder 2026 [bundle:3]; Moawad 2026 [bundle:4]; Mosher 2025 [bundle:5]; Nouni-Garcia 2025 [bundle:9]; Valeriani 2026 [bundle:10]; Wolfe 2025 [bundle:7]); Contextual Adjacent Evidence n=2 (direction: unclear=2; directness: direct=1; indirect=1; sources: Arnreiter 2025 [bundle:8]; Yu 2024 [bundle:6]); Immune and Inflammation n=1 (direction: unclear=1; directness: direct=1; sources: Pistrosch 2021 [bundle:2]); Longevity n=1 (direction: unclear=1; directness: direct=1; sources: Ibrahim 2026 [bundle:1]).", "type": "claim"}, {"id": "claim_29", "text": "| Evidence domain | Source | Direction | Directness | Tier | Evidence role | Finding |", "type": "claim"}, {"id": "claim_30", "text": "| Cardiometabolic | Fransquet 2026: Triglyceride Polygenic Score Identifies Differential Bleeding and Cardiovascular Risk with Aspirin in Primary Prevention | direction=unclear | directness=direct | A1 | outcome=Cardiometabolic; direction=unclear | finding=2 extracted claim(s); receipt-level direction is the coded finding |", "type": "claim"}, {"cited_as": "Ibrahim 2026", "comparator": "not extracted", "directness": "direct", "doi": "10.1186/s12872-026-05708-w", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) represents the primary cause of morbidity and mortality among cases with diabetes. PURPOSE: To determine whether a strategy of ticagrelor monotherapy initiated after 3 months of dual antiplatelet treatment (DAPT) modifies the rate of major adverse cardiovascular effect (MACE) as the primary endpoint and bleeding events as the secondary endpoint, relative to a 12-month regimen of ticagrelor-based DAPT in diabetic cases with acute coronary syndrome (ACS) treated by Percutaneous coronary intervention (PCI). METHODS: This randomized, [excerpt truncated].", "excerpt": "BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) represents the primary cause of morbidity and mortality among cases with diabetes. PURPOSE: To determine whether a strategy of ticagrelor monotherapy initiated after 3 months of dual antiplatelet treatment (DAPT) modifies the rate of major adverse cardiovascular effect (MACE) as the primary endpoint and bleeding events as the secondary endpoint, relative to a 12-month regimen of ticagrelor-based DAPT in diabetic cases with acute coronary syndrome (ACS) treated by Percutaneous coronary intervention (PCI). METHODS: This randomized, open-label study included 400 diabetic patients with acute coronary syndrome (STEMI or NSTEMI) treated with PCI. Patients were randomly assigned to receive ticagrelor monotherapy after 3 months of DAPT or to continue ticagrelor plus aspirin for 12 months. The primary endpoint was major adverse cardiovascular events (MACE), and the secondary endpoint was bleeding events. RESULTS: Hemoglobin level after three month was substantially higher in group 1, the mean ± SD was 12.97 ± 1.7 g/dl while group 2 was 12.6 ± 1.47 g/dl (p = 0.02). Platelet count did not differ markedly between groups.", "id": "source_1", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "some_concerns", "study": "Evaluation of safety and affection of variable duration of dual antiplatelet therapy using aspirin plus ticagrelor after successful percutaneous coronary intervention for diabetic patients with acute coronary syndrome", "type": "source", "url": "https://doi.org/10.1186/s12872-026-05708-w", "year": 2026}, {"cited_as": "Pistrosch 2021", "comparator": "not extracted", "directness": "direct", "doi": "10.1007/s00125-021-05562-9", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "AIMS/HYPOTHESIS: Individuals with type 2 diabetes mellitus and subclinical inflammation have stimulated coagulation, activated platelets and endothelial dysfunction. Recent studies with the direct factor Xa inhibitor rivaroxaban in combination with low-dose aspirin demonstrated a significant reduction of major cardiovascular events, especially in individuals with type 2 diabetes and proven cardiovascular disease. Therefore, we asked the question of whether treatment with rivaroxaban could influence endothelial function, arterial stiffness and platelet activation. METHODS: We conducted a [excerpt truncated].", "excerpt": "AIMS/HYPOTHESIS: Individuals with type 2 diabetes mellitus and subclinical inflammation have stimulated coagulation, activated platelets and endothelial dysfunction. Recent studies with the direct factor Xa inhibitor rivaroxaban in combination with low-dose aspirin demonstrated a significant reduction of major cardiovascular events, especially in individuals with type 2 diabetes and proven cardiovascular disease. Therefore, we asked the question of whether treatment with rivaroxaban could influence endothelial function, arterial stiffness and platelet activation. METHODS: We conducted a multi-centre, prospective, randomised, open-label trial in 179 participants with type 2 diabetes (duration 2-20 years), subclinical inflammation (high-sensitivity C-reactive protein 2-10 mg/l) and at least two traits of the metabolic syndrome to compare the effects of the direct factor Xa inhibitor rivaroxaban (5 mg twice daily) vs aspirin (100 mg every day) on endothelial function (assessed by forearm occlusion plethysmography), skin blood flow (assessed by laser-Doppler fluxmetry), arterial stiffness (assessed by pulse wave velocity) and serum biomarkers of endothelial function and inflammation.", "id": "source_2", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "some_concerns", "study": "Rivaroxaban compared with low-dose aspirin in individuals with type 2 diabetes and high cardiovascular risk: a randomised trial to assess effects on endothelial function, platelet activation and vascular biomarkers", "type": "source", "url": "https://doi.org/10.1007/s00125-021-05562-9", "year": 2021}, {"cited_as": "Holder 2026", "comparator": "not extracted", "directness": "direct", "doi": "10.1186/s12916-026-04654-w", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "BACKGROUND: Evidence for the net benefit of aspirin for primary prevention of cardiovascular disease (CVD) is finely balanced, leading to variation in guideline recommendations internationally. External validity of randomised clinical trial (RCT) evidence may therefore be of particular importance. The aim of this study is to characterise real-world patients according to their eligibility for guideline-cited aspirin RCTs for primary CVD prevention. METHODS: Eligibility criteria from 14 RCTs were applied to a linked primary care/hospital discharge dataset of people ≥ 40 years without CVD. [excerpt truncated].", "excerpt": "BACKGROUND: Evidence for the net benefit of aspirin for primary prevention of cardiovascular disease (CVD) is finely balanced, leading to variation in guideline recommendations internationally. External validity of randomised clinical trial (RCT) evidence may therefore be of particular importance. The aim of this study is to characterise real-world patients according to their eligibility for guideline-cited aspirin RCTs for primary CVD prevention. METHODS: Eligibility criteria from 14 RCTs were applied to a linked primary care/hospital discharge dataset of people ≥ 40 years without CVD. Proportions eligible for each trial were calculated, and characteristics of eligible and ineligible patients compared for each trial, including Cox regression analysis of event rates for major adverse cardiovascular events (MACE), major bleeding events, and non-cardiovascular mortality. RESULTS: Of 570,211 included patients (300,500 [52.7%] women, 336,877 [59%] < 60 years), the median proportion ineligible for 14 RCTs was 90.7% (range 42.5-99.4%) and 24.0% of patients were ineligible for all RCTs. On average, trial-ineligible populations were younger (median age trial-ineligible 57.", "id": "source_3", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "some_concerns", "study": "Eligibility of real-world patients for aspirin primary prevention trials in cardiovascular disease", "type": "source", "url": "https://doi.org/10.1186/s12916-026-04654-w", "year": 2026}, {"cited_as": "Moawad 2026", "comparator": "not extracted", "directness": "review", "doi": "10.1097/MD.0000000000047773", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "BACKGROUND: The optimal choice of antiplatelet monotherapy after dual antiplatelet therapy (DAPT) among patients undergoing PCI remains debatable. While aspirin has long been the default choice, clopidogrel has emerged as a potential alternative due to its lower bleeding risk and possible superior ischemic protection. This meta-analysis sought to investigate the recent findings comparing the use of aspirin against clopidogrel after different durations of DAPT in patients who underwent PCI. METHODS: We searched for randomized controlled trials and cohort studies comparing long-term aspirin and [excerpt truncated].", "excerpt": "BACKGROUND: The optimal choice of antiplatelet monotherapy after dual antiplatelet therapy (DAPT) among patients undergoing PCI remains debatable. While aspirin has long been the default choice, clopidogrel has emerged as a potential alternative due to its lower bleeding risk and possible superior ischemic protection. This meta-analysis sought to investigate the recent findings comparing the use of aspirin against clopidogrel after different durations of DAPT in patients who underwent PCI. METHODS: We searched for randomized controlled trials and cohort studies comparing long-term aspirin and clopidogrel monotherapy after DAPT post-PCI. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes included major and minor bleeding, gastrointestinal (GI) bleeding, stroke, myocardial infarction (MI), target vessel revascularization, and stent thrombosis. RESULTS: Six studies comprising 14,992 patients were included. Clopidogrel monotherapy was associated with a significantly lower risk of MACE than aspirin (risk ratio [RR]: 1.24; 95% CI: 1.09-1.42; P = .001). Aspirin monotherapy resulted in a higher risk of minor bleeding (RR: 1.57; 95% CI: 1.06-2.34; P = .", "id": "source_4", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Antiplatelet dilemma: Clopidogrel or aspirin for long-term cardiovascular protection after dual antiplatelet therapy following PCI", "type": "source", "url": "https://doi.org/10.1097/MD.0000000000047773", "year": 2026}, {"cited_as": "Mosher 2025", "comparator": "not extracted", "directness": "direct", "doi": "10.1161/JAHA.125.043161", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "BACKGROUND: Guidelines recommend aspirin (75-100 mg daily) for the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). However, it is unknown if people with a history of ASCVD and chronic obstructive pulmonary disease (COPD) or asthma, which are independent risk factors for ASCVD, would benefit from higher dose aspirin. METHODS: We evaluated the effectiveness and safety of 2 aspirin doses among individuals with and without COPD/asthma in the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) trial. The ADAPTABLE study was an [excerpt truncated].", "excerpt": "BACKGROUND: Guidelines recommend aspirin (75-100 mg daily) for the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). However, it is unknown if people with a history of ASCVD and chronic obstructive pulmonary disease (COPD) or asthma, which are independent risk factors for ASCVD, would benefit from higher dose aspirin. METHODS: We evaluated the effectiveness and safety of 2 aspirin doses among individuals with and without COPD/asthma in the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) trial. The ADAPTABLE study was an open-label, randomized clinical trial that assigned people with ASCVD to aspirin 81 or 325 mg. We performed a secondary analysis of data from the ADAPTABLE study to investigate the difference in clinical effectiveness and safety among people with and without COPD or asthma randomized to aspirin 325 versus 81 mg. We assessed if history of COPD/asthma modified the association between aspirin dose and outcomes. RESULTS: Among the 14 662 participants, 2778 had a history of COPD or asthma and 11 884 had no history of COPD or asthma.", "id": "source_5", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "some_concerns", "study": "Aspirin Dosing for Secondary Prevention of Atherosclerotic Cardiovascular Disease in Chronic Obstructive Pulmonary Disease and Asthma: Insights From ADAPTABLE", "type": "source", "url": "https://doi.org/10.1161/JAHA.125.043161", "year": 2025}, {"cited_as": "Yu 2024", "comparator": "not extracted", "directness": "direct", "doi": "10.1093/ehjcvp/pvae085", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "During a median 4.6 years of follow-up with randomization to 100 mg/day aspirin vs. placebo, 234 (1.9%) participants had CAD and 373 (3.1%) had bleeding events. In the overall cohort, aspirin resulted in higher bleeding risk [adjusted Hazard ratio (aHR) = 1.30 (1.06-1.61), P = 0.01] but no significant CAD reduction [aHR = 0.84 (0.64-1.09), P = 0.19].", "excerpt": "AIMS: Recent aspirin primary prevention trials failed to identify a net benefit of aspirin for preventing cardiovascular disease vs. the harms of bleeding. This study aimed to investigate whether a high-risk subgroup, individuals with elevated genetic predisposition to coronary artery disease (CAD), might derive more benefit than harm with aspirin, compared to those with lower genetic risk. METHODS AND RESULTS: We performed genetic risk stratification of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized controlled trial using a CAD polygenic risk score (GPSMult). For 12 031 genotyped participants (5974 aspirin, 6057 placebo) overall, we stratified them by GPSMult quintiles (q1-5), then examined risk of CAD (composite of myocardial infarction and coronary heart disease death) and bleeding events using Cox models. During a median 4.6 years of follow-up with randomization to 100 mg/day aspirin vs. placebo, 234 (1.9%) participants had CAD and 373 (3.1%) had bleeding events. In the overall cohort, aspirin resulted in higher bleeding risk [adjusted Hazard ratio (aHR) = 1.30 (1.06-1.61), P = 0.01] but no significant CAD reduction [aHR = 0.84 (0.64-1.09), P = 0.19].", "id": "source_6", "intervention_or_exposure": "not extracted", "population": "not extracted", "quote": "During a median 4.6 years of follow-up with randomization to 100 mg/day aspirin vs. placebo, 234 (1.9%) participants had CAD and 373 (3.1%) had bleeding events. In the overall cohort, aspirin resulted in higher bleeding risk [adjusted Hazard ratio (aHR) = 1.30 (1.06-1.61), P = 0.01] but no significant CAD reduction [aHR = 0.84 (0.64-1.09), P = 0.19].", "risk_of_bias": "some_concerns", "study": "Polygenic risk, aspirin, and primary prevention of coronary artery disease", "type": "source", "url": "https://doi.org/10.1093/ehjcvp/pvae085", "year": 2024}, {"cited_as": "Wolfe 2025", "comparator": "not extracted", "directness": "direct", "doi": "10.1093/eurheartj/ehaf514", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "At enrolment, participants were aged ≥70 years (≥65 years for US minorities) without prior cardiovascular events, dementia, or independence-limiting physical disability. Randomization was to daily low-dose aspirin or matching placebo for the 4.7 years of the trial.", "excerpt": "BACKGROUND AND AIMS: Guidelines recommend against routine initiation of low-dose aspirin in older adults for primary prevention of atherosclerotic cardiovascular disease events. This study aimed to estimate long-term and post-trial effects of aspirin on major adverse cardiovascular events (MACE) and major haemorrhage using extended follow-up of participants from the ASPREE trial. METHODS: In-trial (2010-17) and post-trial (2017-22) data were analysed. At enrolment, participants were aged ≥70 years (≥65 years for US minorities) without prior cardiovascular events, dementia, or independence-limiting physical disability. Randomization was to daily low-dose aspirin or matching placebo for the 4.7 years of the trial. RESULTS: Of the 19 114 participants randomized (9525 aspirin, 9589 placebo), 15 668 without in-trial MACE consented to post-trial follow-up. No long-term benefit of randomization to aspirin was observed for MACE for the entire in-trial and post-trial period [hazard ratio (HR) 1.04, 95% confidence interval (CI) .94, 1.15]. However, during the post-trial period (median 4.3 years), there was a higher rate of MACE (HR 1.17, 95% CI 1.01, 1.", "id": "source_7", "intervention_or_exposure": "not extracted", "population": "not extracted", "quote": "At enrolment, participants were aged ≥70 years (≥65 years for US minorities) without prior cardiovascular events, dementia, or independence-limiting physical disability. Randomization was to daily low-dose aspirin or matching placebo for the 4.7 years of the trial.", "risk_of_bias": "some_concerns", "study": "Aspirin, cardiovascular events, and major bleeding in older adults: extended follow-up of the ASPREE trial", "type": "source", "url": "https://doi.org/10.1093/eurheartj/ehaf514", "year": 2025}, {"cited_as": "Arnreiter 2025", "comparator": "not extracted", "directness": "indirect", "doi": "10.1093/ejcts/ezaf175", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "OBJECTIVES: Patients with extensive coronary artery disease (CAD) have a higher risk of cardiovascular events. This post hoc analysis of the Ticagrelor in CABG (TiCAB) trial examined the association of ticagrelor monotherapy versus aspirin with clinical outcomes after coronary artery bypass grafting (CABG) in relation to the extent of CAD. METHODS: The TiCAB trial randomized CABG patients to ticagrelor (90 mg twice daily) or aspirin (100 mg daily) for 12 months. Patients were stratified by SYNTAX score terciles: low (≤22), intermediate (23-32) and high (≥33). The primary end-point was major [excerpt truncated].", "excerpt": "OBJECTIVES: Patients with extensive coronary artery disease (CAD) have a higher risk of cardiovascular events. This post hoc analysis of the Ticagrelor in CABG (TiCAB) trial examined the association of ticagrelor monotherapy versus aspirin with clinical outcomes after coronary artery bypass grafting (CABG) in relation to the extent of CAD. METHODS: The TiCAB trial randomized CABG patients to ticagrelor (90 mg twice daily) or aspirin (100 mg daily) for 12 months. Patients were stratified by SYNTAX score terciles: low (≤22), intermediate (23-32) and high (≥33). The primary end-point was major adverse cardiac and cerebrovascular events (MACCE) at 12 months, including cardiovascular death, myocardial infarction, stroke or repeat revascularization. Secondary end-points included individual MACCE components and major bleeding events. Cox proportional hazards models were used to assess treatment effects. RESULTS: Among 752 patients, 33.4% had low, 36.0% intermediate and 30.6% high SYNTAX scores (median 26.5 [20.0-33.0]). MACCE rates were similar across groups (low: 7.8%; intermediate: 9.2%; high: 8.8%; P = 0.", "id": "source_8", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Extent of coronary artery disease and clinical outcomes with ticagrelor monotherapy versus aspirin after coronary artery bypass grafting: insights from the TiCAB trial", "type": "source", "url": "https://doi.org/10.1093/ejcts/ezaf175", "year": 2025}, {"cited_as": "Nouni-Garcia 2025", "comparator": "not extracted", "directness": "review", "doi": "10.3389/fcvm.2025.1570331", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "BACKGROUND: Aspirin (acetylsalicylic acid, ASA) is widely recommended for long-term secondary cardiovascular prevention (SCP), but its clinical effectiveness depends on patient adherence, which remains suboptimal. Understanding how adherence and persistence to ASA are measured is essential to improving outcomes. This systematic review aimed to identify the methods used to assess adherence and persistence to ASA in SCP and evaluate their validity indicators. METHODS: We systematically searched EMBASE, MEDLINE, and Scopus for studies published up to October 30, 2023, reporting methods for [excerpt truncated].", "excerpt": "BACKGROUND: Aspirin (acetylsalicylic acid, ASA) is widely recommended for long-term secondary cardiovascular prevention (SCP), but its clinical effectiveness depends on patient adherence, which remains suboptimal. Understanding how adherence and persistence to ASA are measured is essential to improving outcomes. This systematic review aimed to identify the methods used to assess adherence and persistence to ASA in SCP and evaluate their validity indicators. METHODS: We systematically searched EMBASE, MEDLINE, and Scopus for studies published up to October 30, 2023, reporting methods for measuring adherence or persistence to ASA in adults undergoing secondary cardiovascular prevention. Two reviewers independently screened articles and extracted data on study characteristics, measurement methods, and validity indicators. The results were synthesized in tabular form according to method type (indirect or direct) and outcome assessed (adherence or persistence). Risk of bias was evaluated for studies that conducted validation analyses of the measurement methods. RESULTS: Forty studies were included, most conducted in the United States.", "id": "source_9", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Methods and validity indicators for measuring adherence and persistence to aspirin in secondary cardiovascular prevention: a systematic review", "type": "source", "url": "https://doi.org/10.3389/fcvm.2025.1570331", "year": 2025}, {"cited_as": "Valeriani 2026", "comparator": "not extracted", "directness": "review", "doi": "10.1016/j.amjmed.2026.05.016", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "BACKGROUND: Aspirin is a standard therapy for secondary prevention in coronary artery disease, yet its antiplatelet effect varies and incomplete thromboxane-A₂ inhibition has been shown in older individuals. Because no age threshold currently guides treatment, we investigated whether aspirin efficacy differs across predefined age cut-off in patients with coronary artery disease. METHODS: We analyzed data from START-ANTIPLATELET registry, a multicenter prospective registry of patients hospitalized for acute coronary syndrome and subsequently treated with at least one month of aspirin [excerpt truncated].", "excerpt": "BACKGROUND: Aspirin is a standard therapy for secondary prevention in coronary artery disease, yet its antiplatelet effect varies and incomplete thromboxane-A₂ inhibition has been shown in older individuals. Because no age threshold currently guides treatment, we investigated whether aspirin efficacy differs across predefined age cut-off in patients with coronary artery disease. METHODS: We analyzed data from START-ANTIPLATELET registry, a multicenter prospective registry of patients hospitalized for acute coronary syndrome and subsequently treated with at least one month of aspirin monotherapy. Patients were stratified by age ≥ 65 versus < 65 65 years. The primary endpoint was major adverse cardiovascular events, evaluated using Kaplan-Meier estimates and multivariable Cox regression. A systematic review and meta-analysis were conducted to evaluate the effect of aspirin for secondary prevention in older versus younger adults. Pooled risk ratios with 95% confidence intervals were calculated using a random-effects model. RESULTS: 410 patients were included in the registry, of whom 53.7% had ≥ 65 years.", "id": "source_10", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Age-related efficacy of aspirin in secondary prevention of coronary artery disease: START-ANTIPLATELET registry and meta-analysis of randomized trials.", "type": "source", "url": "https://doi.org/10.1016/j.amjmed.2026.05.016", "year": 2026}, {"cited_as": "Fransquet 2026", "comparator": "not extracted", "directness": "direct", "doi": "10.64898/2026.02.19.26346656", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "Participants aged ≥70 years (≥65 years for U.S. minorities) without cardiovascular disease, dementia, or physical disability were randomized to 100 mg daily aspirin or placebo. Among those with high-quality genotyping data (n=13,571; median follow-up 4.6 years), we tested 572 cardiovascular- and hematologic-related PGSs for interaction with aspirin using Cox proportional hazards models, applying Bonferroni correction.", "excerpt": "Aims Low-dose aspirin is no longer routinely recommended for primary prevention in older adults because bleeding risks outweigh cardiovascular benefits. We aimed to investigate whether polygenic scores (PGSs) could modify the effects of aspirin on major bleeding and major adverse cardiovascular events (MACE) in a trial of older individuals. Methods We conducted post-hoc genetic analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized, placebo-controlled trial in Australia and the United States. Participants aged ≥70 years (≥65 years for U.S. minorities) without cardiovascular disease, dementia, or physical disability were randomized to 100 mg daily aspirin or placebo. Among those with high-quality genotyping data (n=13,571; median follow-up 4.6 years), we tested 572 cardiovascular- and hematologic-related PGSs for interaction with aspirin using Cox proportional hazards models, applying Bonferroni correction. Results A triglyceride-related PGS (PGS003144) modified aspirin’s effect on major bleeding (interaction P=5.9×10 −5 ; Bonferroni-adjusted P=0.034). In the lowest PGS quintile, aspirin increased major bleeding compared with placebo (hazard ratio [HR] 2.", "id": "source_11", "intervention_or_exposure": "not extracted", "population": "not extracted", "quote": "Participants aged ≥70 years (≥65 years for U.S. minorities) without cardiovascular disease, dementia, or physical disability were randomized to 100 mg daily aspirin or placebo. Among those with high-quality genotyping data (n=13,571; median follow-up 4.6 years), we tested 572 cardiovascular- and hematologic-related PGSs for interaction with aspirin using Cox proportional hazards models, applying Bonferroni correction.", "risk_of_bias": "some_concerns", "study": "Triglyceride Polygenic Score Identifies Differential Bleeding and Cardiovascular Risk with Aspirin in Primary Prevention", "type": "source", "url": "https://doi.org/10.64898/2026.02.19.26346656", "year": 2026}, {"cited_as": "Berger 2006", "comparator": "not extracted", "directness": "direct", "doi": "10.1001/jama.295.3.306", "effect": "not extracted", "endpoint": "not extracted", "evidence_span": "CONTEXT: Aspirin therapy reduces the risk of cardiovascular disease in adults who are at increased risk. However, it is unclear if women derive the same benefit as men. OBJECTIVE: To determine if the benefits and risks of aspirin treatment in the primary prevention of cardiovascular disease vary by sex. DATA SOURCES AND STUDY SELECTION: MEDLINE and the Cochrane Central Register of Controlled Trials databases (1966 to March 2005), bibliographies of retrieved trials, and reports presented at major scientific meetings. Eligible studies were prospective, randomized controlled trials of aspirin [excerpt truncated].", "excerpt": "CONTEXT: Aspirin therapy reduces the risk of cardiovascular disease in adults who are at increased risk. However, it is unclear if women derive the same benefit as men. OBJECTIVE: To determine if the benefits and risks of aspirin treatment in the primary prevention of cardiovascular disease vary by sex. DATA SOURCES AND STUDY SELECTION: MEDLINE and the Cochrane Central Register of Controlled Trials databases (1966 to March 2005), bibliographies of retrieved trials, and reports presented at major scientific meetings. Eligible studies were prospective, randomized controlled trials of aspirin therapy in participants without cardiovascular disease that reported data on myocardial infarction (MI), stroke, and cardiovascular mortality. Six trials with a total of 95 456 individuals were identified; 3 trials included only men, 1 included only women, and 2 included both sexes. DATA EXTRACTION: Studies were reviewed to determine the number of patients randomized, mean duration of follow-up, and end points (a composite of cardiovascular events [nonfatal MI, nonfatal stroke, and cardiovascular mortality], each of these individual components separately, and major bleeding).", "id": "source_12", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "some_concerns", "study": "Aspirin for the Primary Prevention of Cardiovascular Events in Women and Men", "type": "source", "url": "https://doi.org/10.1001/jama.295.3.306", "year": 2006}], "publication_id": "02840007-a0ce-4dd5-86ff-bcf9cc81d432", "screening": {"excluded": 0, "exclusion_reasons": ["No PRISMA full-text exclusion-stage filter was applied."], "flow": ["identified", "screened", "excluded_with_reasons", "included"], "identified": 12, "included": 12, "included_or_retained": 12, "screened": 12, "wording": "12 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit."}}

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