Abstract and Introduction
Abstract
Background The benefit of aspirin to prevent cardiovascular events in subjects without clinical cardiovascular disease relative to the increased risk of bleeding is uncertain.
Methods A meta-analysis of randomized trials of aspirin versus placebo/control to assess the effect of aspirin on major cardiovascular events (MCEs) (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), individual components of the MCE, stroke subtype, all-cause mortality, and major bleeding. Nine trials involving 102,621 patients were included: 52,145 allocated to aspirin and 50,476 to placebo/control.
Results Over a mean follow-up of 6.9 years, aspirin was associated with a reduction in MCE (risk ratio [RR] 0.90, 95% CI 0.85–0.96, P < .001). There was no significant reduction for myocardial infarction, stroke, ischemic stroke, or all-cause mortality. Aspirin was associated with hemorrhagic stroke (RR 1.35, 95% CI 1.01–1.81, P = .04) and major bleeding (RR 1.62, 95% CI 1.31–2.00, P < .001). In meta-regression, the benefits and bleeding risks of aspirin were independent of baseline cardiovascular risk, background therapy, age, sex, and aspirin dose. The number needed to treat to prevent 1 MCE over a mean follow-up of 6.9 years was 253 (95% CI 163–568), which was offset by the number needed to harm to cause 1 major bleed of 261 (95% CI 182–476).
Conclusions The current totality of evidence provides only modest support for a benefit of aspirin in patients without clinical cardiovascular disease, which is offset by its risk. For every 1,000 subjects treated with aspirin over a 5-year period, aspirin would prevent 2.9 MCE and cause 2.8 major bleeds.
Introduction
Aspirin is effective in decreasing cardiovascular morbidity and mortality in patients with clinical evidence of cardiovascular disease (CVD). Specifically, benefits of aspirin are well defined for secondary prevention of acute myocardial infarction (MI) and stroke, forming the basis for current clinical practice guidelines. These responsive populations include patients who have experienced plaque rupture or vessel occlusion sufficient to induce a symptomatic state (eg, stable angina or transient ischemic attack), acute coronary syndrome, or ischemic stroke. The data demonstrating benefit of aspirin in patients without clinical CVD are less certain. This includes populations at risk based on age, risk factors such as diabetes or hypertension, or evidence of subclinical atherosclerosis. Clinical decision making is further complicated by several meta-analyses of the older trials that found a significant decrease in the composite of major cardiovascular events (MCEs) by approximately 12%, but newer trials of aspirin in patients at high risk but without clinical CVD have failed to achieve their primary end points. Thus, the benefit-to-risk relationship needs further definition in light of the newer evidence.
The most recent meta-analysis reviewed 6 primary prevention trials and concluded that current evidence did not clearly support a net benefit of aspirin relative to the excess bleeding risk in primary prevention. This analysis did not identify any potential subgroups as response modifiers including age, gender, diabetes or other risk factors, or predicted 5-year risk of CVD. However, the publication of 3 new trials in at-risk populations allows for further evaluation of these potential risk modifiers. Thus, the current meta-analysis includes new data and tests the null hypothesis on the available data that there is no net benefit relative to risk for aspirin when used in patients without clinical CVD.