A Randomized Trial of Low-Dose Aspirin in the Primary Prevention of Cardiovascular Disease in Women
Paul M Ridker, M.D., Nancy R. Cook, Sc.D., I-Min Lee, M.B., B.S., David Gordon, M.A., J. Michael Gaziano, M.D., JoAnn E. Manson, M.D., Charles H. Hennekens, M.D., and Julie E. Buring, Sc.D.
Background Randomized trials have shown that low-dose aspirindecreases the risk of a first myocardial infarction in men,with little effect on the risk of ischemic stroke. There arefew similar data in women.
Methods We randomly assigned 39,876 initially healthy women45 years of age or older to receive 100 mg of aspirin on alternatedays or placebo and then monitored them for 10 years for a firstmajor cardiovascular event (i.e., nonfatal myocardial infarction,nonfatal stroke, or death from cardiovascular causes).
Results During follow-up, 477 major cardiovascular events wereconfirmed in the aspirin group, as compared with 522 in theplacebo group, for a nonsignificant reduction in risk with aspirinof 9 percent (relative risk, 0.91; 95 percent confidence interval,0.80 to 1.03; P=0.13). With regard to individual end points,there was a 17 percent reduction in the risk of stroke in theaspirin group, as compared with the placebo group (relativerisk, 0.83; 95 percent confidence interval, 0.69 to 0.99; P=0.04),owing to a 24 percent reduction in the risk of ischemic stroke(relative risk, 0.76; 95 percent confidence interval, 0.63 to0.93; P=0.009) and a nonsignificant increase in the risk ofhemorrhagic stroke (relative risk, 1.24; 95 percent confidenceinterval, 0.82 to 1.87; P=0.31). As compared with placebo, aspirinhad no significant effect on the risk of fatal or nonfatal myocardialinfarction (relative risk, 1.02; 95 percent confidence interval,0.84 to 1.25; P=0.83) or death from cardiovascular causes (relativerisk, 0.95; 95 percent confidence interval, 0.74 to 1.22; P=0.68).Gastrointestinal bleeding requiring transfusion was more frequentin the aspirin group than in the placebo group (relative risk,1.40; 95 percent confidence interval, 1.07 to 1.83; P=0.02).Subgroup analyses showed that aspirin significantly reducedthe risk of major cardiovascular events, ischemic stroke, andmyocardial infarction among women 65 years of age or older.
Conclusions In this large, primary-prevention trial among women,aspirin lowered the risk of stroke without affecting the riskof myocardial infarction or death from cardiovascular causes,leading to a nonsignificant finding with respect to the primaryend point.
Source Information
From the Divisions of Preventive Medicine (P.MR., N.R.C., I-M.L., D.G., J.M.G., J.E.M., J.E.B.), Cardiovascular Medicine (P.MR., J.M.G.), and Aging (J.M.G., J.E.B.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School; the Department of Epidemiology, Harvard School of Public Health (P.MR., N.R.C., I-M.L., J.E.M., J.E.B.); Veterans Affairs Boston Healthcare System (J.M.G.); and the Department of Ambulatory Care and Prevention, Harvard Medical School (J.E.B.) all in Boston; and the Departments of Medicine and Epidemiology and Public Health, University of Miami School of Medicine, and the Department of Biomedical Science, Center of Excellence, Florida Atlantic University, Miami (C.H.H.). This article was published at www.nejm.org on March 7, 2005.
Address reprint requests to Dr. Buring at the Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave. East, Boston, MA 02215, or at jburing{at}rics.bwh.harvard.edu.
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