Clinical trials of direct thrombin and factor Xa inhibitors in atrial fibrillation

Abstract

To review the large phase 3 clinical trials that compare direct thrombin or factor Xa inhibitors with dose-adjusted warfarin in patients with atrial fibrillation who have an increased risk of stroke. In large clinical trials, the oral direct thrombin inhibitor ximelagatran and the long-acting factor Xa inhibitor idraparinux were effective for reducing the risk of thromboembolic stroke, but were not marketed because of liver toxicity and excessive bleeding, respectively. In separate clinical trials, the oral direct thrombin inhibitor dabigatran etexilate and the short-acting oral factor Xa inhibitor rivaroxaban were noninferior or superior to dose-adjusted warfarin for prevention of thromboembolic stroke and systemic embolism, without increasing the risk of bleeding, and were well tolerated. Apixaban, another oral factor Xa inhibitor, is effective in reducing thromboembolic stroke compared with aspirin alone. Results of a trial comparing apixaban with dose-adjusted warfarin are awaited. Dabigatran and rivaroxaban are effective, safe alternatives to dose-adjusted warfarin for reducing thromboembolic risk in patients with atrial fibrillation at high risk of stroke.