A Randomized Trial of Low-Dose Aspirin in the Primary Prevention of Cardiovascular Disease in Women

Abstract

As demonstrated in randomized trials, men who take low-dose aspirin have a smaller risk of a first myocardial infarction (MI) but little change in the risk of ischemic stroke. Because less information is available for women, the investigators randomly assigned 39,876 healthy women 45 years of age or older to receive either 100 mg aspirin or placebo on alternate days and followed them up for 10.1 years on average. The primary end point was a combination of major cardiovascular events, including nonfatal MI, nonfatal stroke, and death from cardiovascular causes. The aspirin-treated women and placebo recipients had similar baseline characteristics. At the end of the trial, there was a nonsignificant 9% decrease in a first major cardiovascular event in women taking aspirin. The risk of stroke was reduced by 17% in the aspirin group (relative risk [RR], 0.83; 95% confidence interval [CI], 0.69–0.99). The risk of ischemic stroke was lowered by 24% (RR, 0.76; 95% CI, 0.63–0.93). The risk of hemorrhagic stroke increased, but not significantly. Fatal stroke was similarly frequent in the aspirin and placebo groups. Aspirin had no significant effect on the risk of fatal or nonfatal MI (RR, 1.02; 95% CI, 0.84–1.25) or death from cardiovascular causes (RR, 0.95; 95% CI, 0.74–1.22). Aspirin therapy was associated with a 22% reduction in transient ischemic attacks (RR, 0.78; 93% CI, 0.64–0.94). It had no significant effect on the risk of coronary revascularization or on death from any cause. Aspirin was most beneficial in lowering the risk of major cardiovascular events in former smokers and those who had never smoked. The most consistent benefit was noted in women who were 65 years of age or older when entering the study. Neither vitamin E treatment nor beta-carotene significantly influenced the effects of aspirin on primary or secondary end points. Both gastrointestinal (GI) bleeding and peptic ulcer were significantly more frequent in women taking aspirin than in the placebo group. The RR of GI bleeding requiring transfusion for aspirin-treated women, compared with those given placebo, was 1.4 (95% CI, 1.07–1.83). Hematuria, easy bruising, and epistaxis were frequent in both groups but slightly more so in women taking aspirin. Two aspirin-treated women and 3 given placebo died of GI bleeding. This large primary prevention trial affirmed a lowered risk of stroke in women taking alternate-day aspirin, but this treatment did not substantially alter the risk of MI or cardiovascular death.