Effect of Aspirin on Vascular and Nonvascular Outcomes: Meta-Analysis of Randomized Controlled Trials

Study Questions:

What is the impact and safety of aspirin on vascular and nonvascular outcomes in primary prevention?


Nine randomized placebo-controlled trials with at least 1,000 participants each, reporting on cardiovascular disease (CVD), nonvascular outcomes, or death were included. Three authors abstracted data. Study-specific odds ratios (ORs) were combined using random-effects meta-analysis. Risks versus benefits were evaluated by comparing CVD risk reductions with increases in bleeding.


During a mean (standard deviation) follow-up of 6.0 (2.1) years involving over 100,000 participants, aspirin treatment reduced total CVD events by 10% (OR, 0.90; 95% confidence interval [CI], 0.85-0.96; number needed to treat, 120), driven primarily by reduction in nonfatal myocardial infarction (MI) (OR, 0.80; 95% CI, 0.67-0.96; number needed to treat, 162). There was no significant reduction in CVD death (OR, 0.99; 95% CI, 0.85-1.15) or cancer mortality (OR, 0.93; 95% CI, 0.84-1.03), and there was increased risk of nontrivial bleeding events (OR, 1.31; 95% CI, 1.14-1.50; number needed to harm, 73). Significant heterogeneity was observed for coronary heart disease and bleeding outcomes, which could not be accounted for by major demographic or participant characteristics.


The authors concluded that despite important reductions in nonfatal MI, aspirin prophylaxis in people without prior CVD does not lead to reductions in either CV death or cancer mortality. Because the benefits are further offset by clinically important bleeding events, routine use of aspirin for primary prevention is not warranted, and treatment decisions need to be considered on a case-by-case basis.


This is a very important meta-analysis whose results demonstrate why large, modern, well-designed clinical trials are necessary prior to invoking guidelines for preventive strategies. We were all fooled by the Physicians’ Health Study. The argument against ‘primary prevention’ for aspirin includes trials focused on diabetics, persons with diabetes and peripheral vascular disease, and noncoronary atherosclerosis, who would normally be considered coronary risk equivalents. I was shocked by the results of these trials, and would have thought they were not worth the effort.

Clinical Topics: Vascular Medicine, Atherosclerotic Disease (CAD/PAD)

Keywords: Coronary Artery Disease, Myocardial Infarction, Follow-Up Studies, Atherosclerosis, Platelet Aggregation Inhibitors, Cardiology, Cardiovascular Diseases, Hemorrhage, Diabetes Mellitus, Peripheral Vascular Diseases

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