Aspirin With or Without Statin in Individuals Without Atherosclerotic Cardiovascular Disease Across Risk Categories.

ABSTRACT

Background: The effects of aspirin in adults without atherosclerotic cardiovascular disease (ASCVD), stratified by statin use across different ASCVD risks, remain uncertain. Objectives: The purpose of this study was to examine the effects of aspirin in adults without ASCVD, stratified by statin use across different ASCVD risks. Methods: We searched databases through March 2022 and selected randomized controlled trials of aspirin without ASCVD and follow-up of ≥1 year. We used random-effects models and estimated relative and absolute risks for cardiovascular outcomes, major bleeding, and mortality over 5 years. We calculated absolute risk differences assuming constant relative risks (RRs) across statin use and ASCVD risks. The Cholesterol Treatment Trialists Collaboration, and the ASCEND (A Study of Cardiovascular Events in Diabetes) trial were used to estimate baseline risks. Results: In 16 trials [171,215 individuals; median age, 64 (Q1-Q3 60-65) years], aspirin vs control reduced myocardial infarction (MI) [RR 0.85 (95% CI 0.77-0.95)] but increased major bleeding [RR 1.48 (95% CI 1.32-1.66)]. Aspirin did not reduce mortality. Statin vs no statin was associated with lower bleeding and MI risk; the bleeding and MI risk were proportional to ASCVD risk. For every 10,000 adults, aspirin reduced MI (very low risk 3 events as monotherapy or 1 event with statin; very high risk 49 events as monotherapy or 37 events with statin) and increased major bleeding (very low risk 21 events as monotherapy or 20 events with statin; very high risk 98 events as monotherapy or 94 events with statin) proportional to baseline ASCVD risk. Conclusions: In adults without ASCVD, concomitant statin appeared to significantly reduce absolute risk reduction for MI associated with aspirin without influencing bleeding risk. The anticipated absolute risk of major bleeding with aspirin exceeds absolute MI benefits for every level of ASCVD risk.