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A fierce competition is under way to develop a replacement for warfarin in the treatment of atrial fibrillation (AF). Dabigatran, a direct thrombin inhibitor, is approved for use in the U.S., and rivaroxaban, a factor Xa inhibitor, was noninferior to warfarin in the preliminary results of the ROCKET AF trial (JW Physicians First Watch Nov 16 2010). Now, apixaban, another factor Xa inhibitor, has been compared with aspirin in an industry-sponsored trial.
The AVERROES investigators randomized 5599 patients with AF and at least one additional risk factor for stroke to apixaban (5 mg twice daily) or aspirin (81–324 mg daily). All patients were considered unsuitable for warfarin treatment, 40% because of prior problems with the drug.
The study was terminated early because of demonstrated superiority of apixaban; mean follow-up was 1.1 years. The rate of the primary outcome — stroke or systemic embolism — was 1.6% per year in the apixaban group versus 3.7% per year in the aspirin group (hazard ratio, 0.45; P<0.001). Major bleeding rates were similar in the two groups (apixaban, 1.4% per year; aspirin, 1.2% per year). The rate of the composite of stroke, systemic embolism, myocardial infarction, death from vascular causes, and major bleeding was 5.3% per year in the apixaban group versus 7.2% per year in the aspirin group (HR, 0.74; P=0.003).
Connolly SJ et al. for the AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med 2011 Feb 10; [e-pub ahead of print]. (http://www.nejm.org/doi/full/10.1056/NEJMoa1007432)
Comment
Direct thrombin inhibitors and factor Xa inhibitors hold real promise for preventing thromboembolic events in patients with AF. Because of its long track record, warfarin will continue to play a pivotal role in AF treatment in the short term. However, in the patient considered a poor candidate for warfarin therapy, these findings indicate that apixaban could join dabigatran (and, probably, rivaroxaban) as a safe and effective alternative. Cost remains a concern; nevertheless, I believe future trials and real-world experience will eventually render warfarin obsolete.