Background: The net benefit of aspirin in prevention of CVD and nonvascular events remains unclear. Our objective was to assess the impact (and safety) of aspirin on vascular and nonvascular outcomes in primary prevention.

Data sources: MEDLINE, Cochrane Library of Clinical Trials (up to June 2011) and unpublished trial data from investigators.

Study selection: Nine randomized placebo-controlled trials with at least 1000 participants each, reporting on cardiovascular disease (CVD), nonvascular outcomes, or death were included.

Data extraction: Three authors abstracted data. Study-specific odds ratios (ORs) were combined using random-effects meta-analysis. Risks vs benefits were evaluated by comparing CVD risk reductions with increases in bleeding.

Results: During a mean (SD) 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% CI, 0.85-0.96; number needed to treat, 120), driven primarily by reduction in nonfatal 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.

Conclusions: Despite important reductions in nonfatal MI, aspirin prophylaxis in people without prior CVD does not lead to reductions in either cardiovascular 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.