Aspirin for Primary Atherosclerotic Cardiovascular Disease Prevention as Baseline Risk Increases: A Meta-Regression Analysis

Background: Aspirin has long had a role in the primary prevention of atherosclerotic cardiovascular disease (ASCVD); however, recent randomized controlled trials (RCTs) have challenged this practice. Despite this, aspirin is still commonly recommended for high-risk primary prevention. We tested the hypothesis that aspirin is more efficacious for the primary prevention of ASCVD as the baseline risk increases. Methods: RCTs that compared aspirin with control for primary prevention and evaluated ASCVD (composite of myocardial infarction and ischemic stroke) and major bleeding were included. Rate ratios (RR) and 95% confidence intervals (CI) were calculated. A regression analysis was performed using the ASCVD event rate in the control arm of each RCT as the moderator. Results: Twelve RCTs were identified with 963,829 patient-years of follow-up. Aspirin was associated with a reduction in ASCVD (4.7 vs 5.3 events per 1000 patient-years; RR 0.86; 95% CI, 0.79-0.92). There was increased major bleeding among aspirin users (2.5 vs 1.8 events per 1000 patient-years; RR 1.41; 95% CI, 1.29-1.54). Regression analysis found no relationship between the log RR of ASCVD or major bleeding and rate of ASCVD in the control arm of each RCT. Conclusion: Aspirin is associated with a reduction in ASCVD when used for primary prevention; however, it is unlikely to be clinically significant given the increase in bleeding. More importantly, aspirin's treatment effect does not increase as ASCVD risk increases, as many hypothesize. There is no suggestion from these data that use of aspirin for higher-risk primary prevention patients is beneficial.