Aspirin for the Prevention of Cardiovascular Events in Patients Without Clinical Cardiovascular Disease: A Meta-Analysis of Randomized Trials
What is the relationship between prevention of cardiovascular events in subjects without clinical cardiovascular disease and the increased risk of bleeding?
A meta-analysis of randomized trials of aspirin versus placebo/control was conducted 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.
Over a mean follow-up of 6.9 years, aspirin was associated with a reduction in MCEs (risk ratio [RR], 0.90; 95% confidence interval [CI], 0.85-0.96; p < 0.001). 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 = 0.04) and major bleeding (RR, 1.62; 95% CI, 1.31-2.00; p < 0.001). 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 one 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 one major bleed of 261 (95% CI, 182-476).
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 MCEs and cause 2.8 major bleeds.
The evidence for routine use of aspirin in middle-aged adults who are at increased risk for coronary disease has been markedly diluted by excellent studies in the last decade. The reasons are not clear, but include the use of modern evidence-based prevention strategies. The two most surprising negative studies were in diabetics and persons with peripheral vascular disease, each of which is considered a coronary risk equivalent. Particularly concerning is the 1/1,500 hemorrhagic stroke attributable to aspirin that seems to be present across all groups.
Keywords: Myocardial Infarction, Follow-Up Studies, Cardiovascular Diseases, Coronary Disease, Risk Factors, Peripheral Vascular Diseases
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