Aspirin Prevents Stroke in Women
and Heart Attack in Men


By Neil Osterweil, Senior Associate Editor, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
January 17, 2006
Also covered by: BBC News, MSNBC

MedPage Today Action Points


STONY BROOK, N.Y., Jan. 17 - When it comes to the role of aspirin in preventing cardiovascular events, men are from heart attacks, and women are from strokes.

For both men and women, aspirin therapy provides significant protection against cardiovascular events, but it works in different ways depending upon gender. Aspirin protects women against ischemic strokes, but not myocardial infarction or death, while it affords men protection against MI, but not strokes or cardiovascular mortality.

Those conclusions are drawn from results of a meta-analysis conducted by David L. Brown, M.D., of the State University of New York here and colleagues at other centers, and published in the Jan. 18 issue of Journal of the American Medical Association.

"This is good news because many of the past studies of the effect of aspirin in preventing cardiovascular events looked only at men, so physicians were reluctant to prescribe aspirin for women because there was little data," said co-author Jeffrey Berger, M.D, of Duke University in Durham, N.C. "But now, the combined data of recent trials involving women demonstrates that women can benefit just as much from aspirin therapy as men."

Although the meta-analysis, which looked at aspirin for primary prevention of cardiovascular events in more than 51,000 women and 44,000 men, found gender differences in the cardiovascular protective effects of aspirin, the relatively small number of strokes occurring among men and heart attacks occurring among women make it difficult to determine whether men and women differ in their physical responses to aspirin, the authors said.

In both sexes the use of aspirin also significantly increased the incidence of major bleeding episodes, the investigators noted.

To determine whether there are gender-based differences in the risks and benefits of aspirin for primary prevention of cardiovascular disease, the authors performed a meta-analysis of randomized controlled trials of aspirin therapy in participants without cardiovascular disease. To be considered for the analysis, the trials also had to include data on MI, stroke, and mortality.

End points included a composite of cardiovascular events (nonfatal MI, nonfatal stroke, and cardiovascular mortality), each of these components separately, and major bleeding.

The authors found that among 51,342 women, there were 1,285 major cardiovascular events: 625 strokes, 469 MIs, and 364 cardiovascular deaths. The use of aspirin in these women was associated with a 12% reduction in cardiovascular events (odds ratio 0.88; 95% confidence interval, 0.79-0.99; P=0.03) and a 17% reduction in stroke (OR, 0.83; 95% CI, 0.70-0.97; P=0.02). In particular, aspirin therapy was associated with a reduced rate of ischemic stroke in women (OR, 0.76; 95% CI, 0.63-0.93; P=0.008). There were no significant effects of aspirin on MI or cardiovascular mortality among women, however.

Among 44,114 men studied, there were 2,047 major cardiovascular events: 597 strokes, 1,023 MIs, and 776 cardiovascular deaths. As in women, aspirin therapy was associated with a 14% reduction in cardiovascular events (OR, 0.86; 95% CI, 0.78-0.94; P=0.01), but men also had a 32% reduction in MI (OR, 0.68; 95% CI, 0.54-0.86; P=0.001). There were no significant effects of aspirin therapy in men on either risk of stroke, however, or on cardiovascular mortality.

In both sexes, aspirin treatment increased the risk of bleeding by about 70%: in women the odds ratio was 1.68; 95% CI, 1.13-2.52 (P=0.01), and in men it was 1.72; 95% CI, 1.35-2.20; (P < 0.001). The predominant site of bleeding was the gastrointestinal tract, the authors noted.

Aspirin therapy for an average duration of 6.4 years will result in an absolute benefit of three fewer cardiovascular events per 1,000 women, and four fewer events per 1,000 men, the investigators wrote.

"Both the beneficial and harmful effects of aspirin should be considered by the physician and patient before initiating aspirin for the primary prevention of cardiovascular disease in both sexes," Dr. Brown and colleagues concluded.

In limitations of the study, in addition to the small number of strokes in men and MIs in women, the authors pointed out that "as in most meta-analyses, these results should be interpreted with caution because aspirin dose, duration of treatment, and lengths of follow-up were not uniform."

In addition, they wrote, a "meta-analysis remains retrospective research that is subject to the methodological deficiencies of the included studies."

Primary source: Journal of the American Medical Association
Source reference: Berger JS et al. Aspirin for the Primary Prevention of Cardiovascular Events in Women and Men: A Sex-Specific Meta-analysis of Randomized Controlled Trials
JAMA. 2006;295:306-313