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A Sex-Specific Meta-analysis of Randomized Controlled Trials

Jeffrey S. Berger, MD, MS; Maria C. Roncaglioni, MD; Fausto Avanzini, MD; Ierta Pangrazzi, MD; Gianni Tognoni, MD; David L. Brown, MD

JAMA. 2006;295:306-313.

Context  Aspirin therapy reduces the risk of cardiovascular disease in adults who are at increased risk. However, it is unclear if women derive the same benefit as men.

Objective  To determine if the benefits and risks of aspirin treatment in the primary prevention of cardiovascular disease vary by sex.

Data Sources and Study Selection  MEDLINE and the Cochrane Central Register of Controlled Trials databases (1966 to March 2005), bibliographies of retrieved trials, and reports presented at major scientific meetings. Eligible studies were prospective, randomized controlled trials of aspirin therapy in participants without cardiovascular disease that reported data on myocardial infarction (MI), stroke, and cardiovascular mortality. Six trials with a total of 95 456 individuals were identified; 3 trials included only men, 1 included only women, and 2 included both sexes.

Data Extraction  Studies were reviewed to determine the number of patients randomized, mean duration of follow-up, and end points (a composite of cardiovascular events [nonfatal MI, nonfatal stroke, and cardiovascular mortality], each of these individual components separately, and major bleeding).

Data Synthesis  Among 51 342 women, there were 1285 major cardiovascular events: 625 strokes, 469 MIs, and 364 cardiovascular deaths. Aspirin therapy was associated with a significant 12% reduction in cardiovascular events (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.79-0.99; P = .03) and a 17% reduction in stroke (OR, 0.83; 95% CI, 0.70-0.97; P = .02), which was a reflection of reduced rates of ischemic stroke (OR, 0.76; 95% CI, 0.63-0.93; P = .008). There was no significant effect on MI or cardiovascular mortality. Among 44 114 men, there were 2047 major cardiovascular events: 597 strokes, 1023 MIs, and 776 cardiovascular deaths. Aspirin therapy was associated with a significant 14% reduction in cardiovascular events (OR, 0.86; 95% CI, 0.78-0.94; P = .01) and a 32% reduction in MI (OR, 0.68; 95% CI, 0.54-0.86; P = .001). There was no significant effect on stroke or cardiovascular mortality. Aspirin treatment increased the risk of bleeding in women (OR, 1.68; 95% CI, 1.13-2.52; P = .01) and in men (OR, 1.72; 95% CI, 1.35-2.20; P<.001).

Conclusions  For women and men, aspirin therapy reduced the risk of a composite of cardiovascular events due to its effect on reducing the risk of ischemic stroke in women and MI in men. Aspirin significantly increased the risk of bleeding to a similar degree among women and men.

Author Affiliations: Department of Cardiovascular Medicine, Duke University, Durham, NC (Dr Berger); Department of Cardiovascular Medicine, Instituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy (Drs Roncaglioni, Avanzini, Pangrazzi, and Tognoni); and Division of Cardiovascular Medicine, School of Medicine, State University of New York, Stony Brook (Dr Brown).

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