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Warfarin effective for stroke prevention in patients with atrial fibrillation

The JAMA Network Journals

The blood thinner warfarin can be safely and effectively used to prevent stroke in patients with atrial fibrillation, according to an article in the November 26 issue of The Journal of the American Medical Association (JAMA).

According to background information in the article, multiple randomized clinical trials have demonstrated warfarin therapy to be highly effective in reducing the risk of ischemic stroke in patients with atrial fibrillation (an electrical rhythm disturbance of the heart that causes an irregular heartbeat). In these trials, treatment was associated with relatively low rates of bleeding, which is the major possible adverse effect of warfarin treatment. However, concerns persist about the effectiveness and safety of warfarin in persons treated in usual clinical care since the randomized trials enrolled highly selected patients, included few very elderly patients, and closely monitored patients' level of anticoagulation. This has important clinical implications since atrial fibrillation occurs commonly, particularly among the elderly.

Alan S. Go, M.D., of Kaiser Permanente of Northern California, Oakland, Calif., and colleagues evaluated the effect of warfarin on risk of thromboembolism (the blocking of a blood vessel, e.g., in the brain, by a blood clot), hemorrhage, and death in patients with atrial fibrillation within a usual care setting. The study was conducted between July 1, 1996, and December 31, 1997, with follow-up through August 31, 1999, in a large integrated health care system in Northern California. Of 13,559 adults with atrial fibrillation (not due to a problem with a heart valve), 11,526 were studied, 43 percent of whom were women. The average age was 71 years.

Among 11,526 patients, 397 thromboembolic events (372 ischemic strokes) occurred, and warfarin therapy was associated with a 51 percent lower risk of thromboembolism and stroke compared with no warfarin therapy (either no antithrombotic therapy or aspirin) after adjusting for potential confounders and likelihood of receiving warfarin.

"Warfarin was effective in reducing thromboembolic risk in the presence or absence of risk factors for stroke," the authors write. An "analysis estimated a 64 percent reduction in odds of thromboembolism with warfarin compared with no antithrombotic therapy. Warfarin was also associated with a reduced risk of all-cause mortality [death, 31 percent lower risk]. Intracranial hemorrhage [bleeding into the brain] was uncommon, but the rate was moderately higher among those taking vs. not taking warfarin. However, warfarin therapy was not associated with an increased adjusted risk of nonintracranial major hemorrhage."

"Our results materially extend ... prior findings by providing contemporary and precise estimates of thromboembolism and hemorrhage rates in a broad population of individuals with atrial fibrillation, along with more complete adjustment for potential confounders and attempts to control for the likelihood of receiving warfarin over time," they write.

"Overall, our results demonstrate that findings of the randomized trials of anticoagulation for atrial fibrillation translate well into clinical practice. Our study adds further support for the routine use of anticoagulation for eligible patients with atrial fibrillation who are at moderate to high risk for stroke, particularly when well-organized management of anticoagulation can be provided," the researchers conclude. (JAMA. 2003;290:2685-2692. Available post-embargo at


Editor's Note: This work was supported by a Public Health Services research grant from the National Institute on Aging and the Eliot B. and Edith C. Shoolman Fund of Massachusetts General Hospital. Co-author Elaine M. Hylek, M.D., M.P.H., has received grant support and speaker honoraria from Bristol-Myers Squibb, and co-author Daniel E. Singer, M.D., has received research support from Bristol-Myers Squibb.

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