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Aspirin for Primary Atherosclerotic Cardiovascular Disease Prevention as Baseline Risk Increases: A Meta-Regression
Matthew Nudy1, Jennifer Cooper2, Mehrdad Ghahramani1
1Division of Cardiology, Penn State Heart and Vascular Institute, Hershey, PA.
Insights
Aspirin use for primary prevention of atherosclerotic cardiovascular disease (ASCVD) offers minimal benefit and increases bleeding risk. Its effectiveness does not increase with higher baseline ASCVD risk, challenging current recommendations.
Area of Science:
- Cardiology
- Preventive Medicine
- Clinical Trials
Background:
- Aspirin has historically been recommended for primary prevention of atherosclerotic cardiovascular disease (ASCVD).
- Recent randomized controlled trials (RCTs) have questioned the efficacy of this practice.
- Current guidelines often still recommend aspirin for high-risk individuals.
Purpose of the Study:
- To test the hypothesis that aspirin's efficacy in primary ASCVD prevention increases with higher baseline risk.
- To evaluate the balance between ASCVD risk reduction and major bleeding events with aspirin use.
Main Methods:
- Systematic review and meta-analysis of RCTs comparing aspirin with control for primary ASCVD prevention.
- Assessment of composite ASCVD events (myocardial infarction, ischemic stroke) and major bleeding.
- Regression analysis to explore the relationship between baseline ASCVD risk and treatment effects.
Main Results:
- Twelve RCTs involving over 960,000 patient-years were analyzed.
- Aspirin showed a modest reduction in ASCVD events (RR 0.86; 95% CI, 0.79-0.92).
- Aspirin significantly increased major bleeding risk (RR 1.41; 95% CI, 1.29-1.54).
- No correlation was found between baseline ASCVD event rate and the effect of aspirin on ASCVD or bleeding.
Conclusions:
- Aspirin provides a small ASCVD reduction in primary prevention, outweighed by increased bleeding risk.
- Aspirin's treatment effect for ASCVD prevention does not escalate with increasing baseline risk.
- Current data do not support using aspirin for primary prevention in higher-risk populations.
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.
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