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Background Vitamin K antagonists reduce the risk of stroke in patients with atrial fibrillation but are considered unsuitable in many patients, who usually receive aspirin instead. We investigated the hypothesis that the addition of clopidogrel to aspirin would reduce the risk of vascular events in patients with atrial fibrillation.
Methods A total of 7554 patients with atrial fibrillation who had an increased risk of stroke and for whom vitamin K–antagonist therapy was unsuitable were randomly assigned to receive clopidogrel (75 mg) or placebo, once daily, in addition to aspirin. The primary outcome was the composite of stroke, myocardial infarction, non–central nervous system systemic embolism, or death from vascular causes.
Results At a median of 3.6 years of follow-up, major vascular events had occurred in 832 patients receiving clopidogrel (6.8% per year) and in 924 patients receiving placebo (7.6% per year) (relative risk with clopidogrel, 0.89; 95% confidence interval [CI], 0.81 to 0.98; P=0.01). The difference was primarily due to a reduction in the rate of stroke with clopidogrel. Stroke occurred in 296 patients receiving clopidogrel (2.4% per year) and 408 patients receiving placebo (3.3% per year) (relative risk, 0.72; 95% CI, 0.62 to 0.83; P<0.001). Myocardial infarction occurred in 90 patients receiving clopidogrel (0.7% per year) and in 115 receiving placebo (0.9% per year) (relative risk, 0.78; 95% CI, 0.59 to 1.03; P=0.08). Major bleeding occurred in 251 patients receiving clopidogrel (2.0% per year) and in 162 patients receiving placebo (1.3% per year) (relative risk, 1.57; 95% CI, 1.29 to 1.92; P<0.001).
Conclusions In patients with atrial fibrillation for whom vitamin K–antagonist therapy was unsuitable, the addition of clopidogrel to aspirin reduced the risk of major vascular events, especially stroke, and increased the risk of major hemorrhage. (ClinicalTrials.gov number, NCT00249873
[ClinicalTrials.gov]
.)
Source Information
The members of the writing group (Stuart J. Connolly and Janice Pogue, Population Health Research Institute, Hamilton, ON, Canada; Robert G. Hart, University of Texas Health Center, San Antonio; Stefan H. Hohnloser, Goethe University Hospital, Frankfurt, Germany; Marc Pfeffer, Brigham and Women's Hospital, Boston; and Susan Chrolavicius and Salim Yusuf, Population Health Research Institute, Hamilton, ON, Canada) of Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE) assume responsibility for the overall content and integrity of the article.
This article (10.1056/NEJMoa0901301) was published at NEJM.org on March 31, 2009.
Address reprint requests to Dr. Connolly at the Population Health Research Institute, McMaster University, 237 Barton St. E., Hamilton, ON L8L 2X2, Canada, or at stuart.connolly{at}phri.ca.
Related Letters:
Clopidogrel plus Aspirin in Atrial Fibrillation
Pisters R., Dinh T., Crijns H. J., Chua D., Legal M., Shalansky S. J., Richard T., Butaffuoco F., Vanhaeverbeek M., Goldstein L. B., Lee Y. E., DeZee K. J., Shalimar S., Pangtey G. S., Singh K. K., Connolly S. J., Yusuf S., Hart R. G., the ACTIVE Steering Committee
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N Engl J Med 2009;
361:1312-1315, Sep 24, 2009.
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