Aspirin as preventive therapy in patients with asymptomatic vascular disease.

cause of death in the western world and a leading cause of death worldwide. Assessing patients’ cardiovascular risk may be used to target preventive treatments to asymptomatic individuals at high risk for future CVD events. For these high-risk individuals, strategies including medication, diet, and comprehensive lifestyle approaches have been shown to improve cardiovascular morbidity and mortality. 1 Antiplatelet therapy has long been a cornerstone in the prevention and treatment of CVD. In a systematic overview and meta-analysis, the Antiplatelet Trialists’ Collaboration demonstrated that antiplatelet therapy was associated with reduced rates of myocardial infarction (MI), stroke, and death. 2 The strong data that support aspirin as a therapeutic intervention are in the setting of acute MI or stroke. In the Second International Study of Infarct Survival (ISIS-2), which included patients with suspected MI, aspirin reduced the rate of early vascular mortality by 23% vs placebo (P.001). 3 Similarly, a combined analysis of 2 large stroke trials (International Stroke Trial and Chinese Acute Stroke Trial) found that low-dose aspirin was associated with a significant reduction in recurrent ischemic stroke and mortality. 4 A meta-analysis of 6 trials involving patients with symptomatic stable CVD demonstrated a consistent association between aspirin therapy and reduction of cardiovascular morbidity and mortality. 5 These benefits of aspirin in patients with established CVD, along with the low cost of aspirin therapy, have been extrapolated to high-risk patients without established CVD in an effort to reduce the risk of cardiovascular events. However, preventive therapy presupposes a threat that can be averted at an acceptable risk. In the case of aspirin, the major risk is bleeding. In this issue of JAMA, Fowkes and colleagues 6 report the results of the Aspirin for Asymptomatic Atherosclerosis trial. In this double-blind randomized trial, 3350 patients aged 50 to 75 years without clinically evident CVD but with a screening-detected ankle brachial index (ABI) of 0.95 or less were randomly assigned to receive aspirin (enteric coated 100 mg/d) or placebo. After a mean (SD) follow-up of 8.2 (1.6) years, aspirin was no more effective than placebo at reducing the primary end point of a fatal or nonfatal coronary event, stroke, or revascularization and had no significant effect on any of the secondary end points. Aspirin therapy was, however, associated with a statistically nonsignificant increased risk of major hemorrhage (2.0% vs 1.2%, hazard ratio [HR], 1.71, 95% confidence interval, 0.99-2.97). Intracranial hemorrhage occurred in 11 participants (including 3 fatal subarachnoid/subdural hemorrhages) in the aspirin group and 7 in the placebo group. The results of the trial raise an important question about preventing cardiovascular events—should aspirin be used inprimaryprevention? Althoughthepopulationstudiedhad subclinical atherosclerosis as determined by the ABI, participants had no previous history of CVD events. Thus the goal remains the same—prevention of a first cardiovascular event. The findings of the trial are consistent with those of previous primary prevention trials. The lower boundary of the 95% confidence interval cannot rule out a 16% benefit or exclude a 27% increase in harm. Meta-analyses on theefficacyofaspirininprimarypreventionshowedamodest 12% benefit. 7,8