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Published on: July 21, 2023
Aspirin for primary prevention of cardiovascular disease: a meta-analysis with a particular focus on subgroups
Georg Gelbenegger1, Marek Postula2, Ladislav Pecen3
1Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Insights
Aspirin does not lower mortality for primary prevention of cardiovascular disease (CVD) and increases bleeding risk. The benefit-risk ratio is insufficient, though some subgroups like non-smokers may see reduced major adverse cardiovascular events (MACE).
Area of Science:
- Cardiology
- Preventive Medicine
- Clinical Trials
Background:
- The efficacy of aspirin in primary prevention of cardiovascular disease (CVD) is not well-established.
- Investigating the benefit-risk balance of aspirin for primary CVD prevention is crucial, especially in specific patient subgroups.
Purpose of the Study:
- To conduct a meta-analysis of randomized controlled trials (RCTs) to evaluate the benefit-risk ratio of aspirin for primary CVD prevention.
- To identify subgroups that may benefit more or less from aspirin therapy.
Main Methods:
- A meta-analysis of 13 RCTs involving 164,225 patients was performed.
- Primary efficacy outcome was all-cause mortality; secondary outcomes included cardiovascular mortality, major adverse cardiovascular events (MACE), myocardial infarction, ischemic stroke, and net clinical benefit.
- Primary safety outcome was major bleeding, with subgroup analyses for sex, statin use, diabetes, and smoking.
Main Results:
- Aspirin did not significantly alter all-cause or cardiovascular mortality compared to control.
- Aspirin reduced the risk of MACE (9%), myocardial infarction (14%), and ischemic stroke (10%) but increased major bleeding risk by 46%.
- No net clinical benefit was observed when adjusted for event-associated mortality risk. Significant risk reduction for MACE was noted in patients on statins, non-smokers, and males.
Conclusions:
- Aspirin is not recommended for primary prevention of CVD due to insufficient benefit-risk ratio and lack of mortality reduction.
- Subgroup analyses indicate potential benefits in reducing MACE for non-smokers, patients on statin therapy, and males.
Background:
The role of aspirin in primary prevention of cardiovascular disease (CVD) remains unclear. We aimed to investigate the benefit-risk ratio of aspirin for primary prevention of CVD with a particular focus on subgroups.
Methods:
Randomized controlled trials comparing the effects of aspirin for primary prevention of CVD versus control and including at least 1000 patients were eligible for this meta-analysis. The primary efficacy outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, major adverse cardiovascular events (MACE), myocardial infarction, ischemic stroke, and net clinical benefit. The primary safety outcome was major bleeding. Subgroup analyses involving sex, concomitant statin treatment, diabetes, and smoking were performed.
Results:
Thirteen randomized controlled trials comprising 164,225 patients were included. The risk of all-cause and cardiovascular mortality was similar for aspirin and control groups (RR 0.98; 95% CI, 0.93-1.02; RR 0.99; 95% CI, 0.90-1.08; respectively). Aspirin reduced the relative risk (RRR) of major adverse cardiovascular events (MACE) by 9% (RR 0.91; 95% CI, 0.86-0.95), myocardial infarction by 14% (RR 0.86; 95% CI, 0.77-0.95), and ischemic stroke by 10% (RR 0.90; 95% CI, 0.82-0.99), but was associated with a 46% relative risk increase of major bleeding events (RR 1.46; 95% CI, 1.30-1.64) compared with controls. Aspirin use did not translate into a net clinical benefit adjusted for event-associated mortality risk (mean 0.034%; 95% CI, - 0.18 to 0.25%). There was an interaction for aspirin effect in three patient subgroups: (i) in patients under statin treatment, aspirin was associated with a 12% RRR of MACE (RR 0.88; 95% CI, 0.80-0.96), and this effect was lacking in the no-statin group; (ii) in non-smokers, aspirin was associated with a 10% RRR of MACE (RR 0.90; 95% CI, 0.82-0.99), and this effect was not present in smokers; and (iii) in males, aspirin use resulted in a 11% RRR of MACE (RR 0.89; 95% CI, 0.83-0.95), with a non-significant effect in females.
Conclusions:
Aspirin use does not reduce all-cause or cardiovascular mortality and results in an insufficient benefit-risk ratio for CVD primary prevention. Non-smokers, patients treated with statins, and males had the greatest risk reduction of MACE across subgroups.
Systematic Review Registration:
PROSPERO CRD42019118474.
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