Apixaban versus Warfarin in Patients with Atrial Fibrillation

作者：Christopher B. Granger, John Hunter Alexander, John J.V. McMurray, Renato D. Lópes, Elaine M. Hylek, Michael G. Hanna, Hussein R. Al‐Khalidi, Jack Ansell, Dan Atar, Álvaro Avezum, Maria Cecilia Bahit, Rafael Díaz, J. Donald Easton, Justin Adrian Ezekowitz, Greg C. Flaker, David García, Margarida Geraldes, Bernard John Gersh, Golitsyn Sp, Shinya Goto, Antonio G. Hermosillo, Stefan Hans Hohnloser, John David Horowitz, Puneet Mohan, Petr Janský, Basil S. Lewis, Jose Luis Lopez-Sendon, Prem Pais, Alexander N. Parkhomenko, Freek W.A. Verheugt, Jun Zhu, Lars C. Wallentin · 发表于：New England Journal of Medicine · 年份：2011 · DOI：10.1056/nejmoa1107039 · 被引用次数：9001 · 研究领域：Atrial Fibrillation Management and Outcomes、Vitamin K Research Studies、Intracerebral and Subarachnoid Hemorrhage Research

BACKGROUND: Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. METHODS: In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. RESULTS: The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24...