Hemorrhagic Complications Associated With Aspirin
Authors: Jolanta M. Siller-Matula
Journal: JAMA (2012)

ASPIRIN IS WIDELY USED FOR PRIMARY AND SECONDary prevention of cardiovascular events. Substantial scientific evidence supports the beneficial role of aspirin in reducing the risk of cardiovascular events in secondary prevention. In a meta-analysis including 135 000 patients considered to be at high risk for vascular events (90% with known coronary artery disease, cerebral artery disease, or peripheral artery disease), aspirin was associated with a reduced relative risk of vascular events (myocardial infarction, stroke, and vascular death) by 22% (absolute risk reduction [ARR], 2.5%) but also was associated with an increased relative risk of major extracranial bleeding events by 60% (absolute risk increase [ARI], 0.42%). In another meta-analysis, aspirin used for secondary prevention was associated with a reduced relative risk of myocardial infarction by 31%, ischemic stroke by 22%, and cardiovascular death by 13%. For a hypothetical group of 10 000 patients, aspirin used for secondary prevention would be expected to prevent approximately 250 major vascular events (number needed to treat [NNT], 40) but would be expected to cause approximately 40 major extracranial bleeding events (number needed to harm [NNH], 240). Thus, the net benefit of aspirin for secondary prevention would substantially exceed the bleeding hazard. For 6 major vascular events prevented, approximately 1 major bleeding event would occur; therefore, the value of aspirin for secondary prevention is not disputed. In contrast, there is an ongoing debate surrounding use of aspirin for primary prevention. Published evidence does not support the assumption that the balance of benefits and harms of aspirin use is clearly favorable for primary prevention. In a meta-analysis using individual patient data from 6 randomized trials including 95 000 patients, aspirin was associated with a reduced relative risk of vascular events by 12% (ARR, 0.07%), but also was associated with an increased relative risk of extracranial bleeding events by 54% (ARI, 0.03%). Although aspirin was associated with reduced relative risk of myocardial infarction by 23% (ARR, 0.05%), there was no association between aspirin use and risk of stroke or vascular death. The proportional reduction of vascular events by aspirin in primary prevention was not affected by the predicted risk of coronary heart disease, age, sex, hypertension, or diabetes. For a hypothetical group of 10 000 patients, aspirin use for primary prevention would be expected to prevent 7 major vascular events (NNT, 1430) and cause 1 hemorrhagic stroke and 3 major extracranial bleeding events (NNH, 2500). This suggests that for 2 major vascular events prevented, approximately 1 major bleeding event would occur. A meta-analysis that focused on primary prevention suggested that the effects of aspirin were sex-related: aspirin was associated with a reduced relative risk of stroke by 24% among women and reduced relative risk of myocardial infarction by 32% among men, but these risk reductions were offset by an increase in the relative risk of major bleeding events by 68% among women and 72% among men. Another meta-analysis and a randomized trial support the findings that the magnitude of benefit with aspirin in primary prevention is small and at least partially balanced by the magnitude of harm. Before these clinical trial data were available, the US Preventive Services Task Force recommended use of aspirin for men aged 45 to 79 years and for women aged 55 to 79 years when the potential benefit due to a reduction in myocardial infarction outweighs the potential harm due to an increase in gastrointestinal hemorrhage. These recommendations seem to be mainly based on evidence extrapolated from large trials of populations at high risk of vascular events, under the assumption that age confers an elevated risk of cardiovascular disease. In light of more recent reports, the new European guidelines on cardiovascular disease prevention do not recommend aspirin for primary prevention because of its unfavorable risk-to-benefit profile. In this issue of JAMA, findings from the study by De Berardis et al reinforce the European recommendations for aspirin use. The authors performed a population-based co-