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Dabigatran for stroke in patients with nonvalvular atrial fibrillation

Dabigatran, a direct thrombin inhibitor, recently was approved for prevention of stroke in patients with nonvalvular atrial fibrillation. The evidence for its benefit is strong enough that the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society recently upgraded their atrial fibrillation guidelines to include dabigatran (Circulation published online February 14, 2011). Meanwhile, the direct factor Xa inhibitor rivaroxaban is working its way through the FDA approval process for the same indication, with approval expected later this year. The latest player in the field is apixaban, also a direct factor Xa inhibitor. Apixaban was studied in a double-blind Phase 3 study of 5599 patients with atrial fibrillation who were at increased risk for stroke and for whom vitamin K antagonist therapy was unsuitable. Patients were randomized to receive apixaban 5 mg twice daily or aspirin 81-324 mg per day with a mean follow-up of 1.1 years. The primary outcome was occurrence of stroke or systemic embolism. The study was terminated early because of a clear benefit in favor of apixaban. There were 51 events (1.6 % per year) in the apixaban group vs 113 events (3.7% per year) in the aspirin group (hazard ratio with apixaban 0.45, 95% confidence interval 0.32-0.62; P < 0.001). The death rate was 3.5% in the apixaban group vs 4.4% in the aspirin group (P = 0.07). The rates of major bleeding or intracranial hemorrhage were similar; however, the risk of first hospitalization for cardiovascular causes was significantly lower with apixaban. The authors suggest that apixaban is more effective than aspirin. In indirect comparisons, apixaban is more effective than aspirin plus clopidogrel and at least as effective as warfarin in preventing stroke or systemic embolism in patients with atrial fibrillation (N Engl J Med published online February 10, 2011). Apixaban is currently being studied head-to-head with warfarin in the ARISTOTLE trial. If the data from that trial looks favorable, it is likely that both apixaban and rivaroxaban also will be approved for this indication in the not-too-distant future. Dabigatran and apixaban are both dosed bid while rivaroxaban is a once-a-day drug. The extent to which these drugs gain general usage at the expense of warfarin in large part will be due to patient preference and cost.