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Am Fam Physician. 2003;67(6):1349

While some studies suggest that warfarin is superior to aspirin, aspirin is the more commonly used antithrombotic therapy following myocardial infarction (MI). Hurlen and associates present data on a randomized trial of warfarin, aspirin, or a combination of both to prevent subsequent cardiovascular events in patients with MI.

The Warfarin, Aspirin, Reinfarction Study (WARIS-II) drew its participants from a pool of patients hospitalized for heart attack at 20 different medical centers in Norway. Patients were excluded if they were more than 75 years of age, had any malignancy, or were deemed unlikely to comply with therapy. A total of 3,630 patients were enrolled and randomized to receive warfarin therapy alone (with the goal of achieving an International Normalized Ratio [INR] of 2.8 to 4.2), aspirin alone, or both agents (in this case, the goal INR was lowered to 2.0 to 2.5). Patients were followed on treatment for subsequent cardiovascular disease (repeat MI, stroke, or death). The mean duration of follow-up was approximately four years.

Repeat MI occurred in 9.7 percent of patients who were taking aspirin alone, 7.4 percent of those taking warfarin alone, and 5.7 percent of those taking both medications. Stroke occurred in 2.7 percent of aspirin patients, 1.4 percent of warfarin patients, and 1.4 percent of those taking both agents. Overall mortality was essentially unchanged at 7.6 percent in those taking aspirin, 7.9 percent in those taking warfarin, and 7.9 percent in the combination therapy group.

Withdrawal from the assigned treatment, chiefly because of adverse effects or patient reluctance, was most common in the combination group (13.1 percent), followed by the warfarin-alone group (10.9 percent), and the aspirin-alone group (1.6 percent). Major bleeding occurred most often in those taking warfarin (2.7 percent), followed by combination therapy (2.3 percent, where the goal INR was lower) and the aspirin-alone group (0.7 percent).

The authors conclude that warfarin, alone or in combination therapy, was more effective than aspirin alone in preventing subsequent cardiovascular events in patients with MI but was associated with a greater risk of bleeding.

editor’s note: This study echoes the findings in most studies of warfarin for treatment of atrial fibrillation. A modest reduction in thromboembolic disease occurs, but at a higher price in terms of the patient’s ability to continue therapy and an increased risk of major bleeding. Combining the study end points of reinfarction, stroke, and death shows an absolute risk reduction of 3.3 percent with warfarin alone and 5.0 percent for combination therapy, compared with aspirin. Whether this reduction outweighs the increased rates of patient withdrawal from treatment and the major bleeding that occur with use of warfarin would seem to be a point in the eye of the beholder.—b.z.

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