Aspirin as Preventive Therapy in Patients With Asymptomatic Vascular Disease

Abstract

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