ACTIVE-W: Terminated early, oral coagulants remain optimal treatment for atrial fibrillation
A 47% excess risk of stroke, myocardial infarction, and other vascular events in patients with atrial fibrillation (AF) receiving clopidogrel plus aspirin, compared to warfarin, led to the early termination of ACTIVE-W by the study’s Data and Safety Monitoring Board. Dr. Stuart J. Connolly, McMaster University, Hamilton, Canada, presented the trial at the 2005 Scientific Sessions of the American Heart Association, held in Dallas, Texas from November 13-16. Two other arms of the ACTIVE study program are continuing, one of which is studying the effect of blood pressure lowering on AF.
ACTIVE –W with more than 6500 patients with AF and at least 1 additional risk factor were randomized to clopidogrel plus or aspirin or oral anticoagulation (usually with warfarin).
The primary endpoint of stroke, myocardial infarction, embolism, and vascular death, was 5.6% in the clopidogrel plus aspirin group and 3.9% in the warfarin group, a 47% relative increase with clopidogrel plus aspirin, Connolly said.
Additionally, no reduction in bleeding was found with clopidogrel plus aspirin compared to warfarin.
More than 75% of patients already had received warfarin at the start of the study. “We found that there were important differences in the treatment effects between the patients who had been on warfarin at baseline and those who were not, especially related to bleeding risk, Connolly said. A 36% excess risk for major bleeding was seen in patients on clopidogrel plus aspirin who were warfarin naïve. But, in patients who had take warfarin previously, major bleeding was reduced by 37% on clopidogrel plus aspirin.
“Anticoagulants such as warfarin are superior to clopidogrel plus aspirin for prevention of vascular events in patients with atrial fibrillation,” said Connolly. “Our study does not adequately address the question of whether this is true in patients without previous exposure to warfarin, but there is evidence that the situation may be different in those patients,” and he noted that the ACTIVE-A study will provide additional information about this.
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