A Phase 3, Randomized, Double-Blind, Double-Dummy, Parallel Group, Multi-Center, Multi-National Study For Evaluation Of Efficacy And Safety Of Study Drug Versus Warfarin In Subjects With Atrial Fibrillation

Atrial fibrillation (AF) is the most common type of arrhythmia in adults and becomes more common with increased age. The prevalence is 1% among those aged 60 years or less, and increases to more than 8% in those aged more than 80 years. Subjects with AF are at increased risk for thromboembolic disease and usually receive chronic anti-coagulation. Vitamin K antagonists (e.g., VKAs such as coumarins and indanediones) are commonly used as anticoagulant medications to reduce the risk of stroke and thromboembolic complications in subjects with AF. These anticoagulant agents are indirect thrombin inhibitors which act by blocking the vitamin K-dependent liver production of plasma clotting factors prothrombin (Factor II) and Factors VII, IX, and X. They were the only oral anticoagulants available for over 50 years. Randomized controlled studies have shown that warfarin, the most commonly used VKA, reduces the risk of ischemic stroke in subjects with AF by 65%. However, the use of warfarin is complicated by several inherent problems, including a delayed onset of antithrombotic action, narrow therapeutic index that requires close anticoagulation monitoring using the international normalized ratio (INR), and unpredictable and variable pharmacological response. In addition, numerous drugs, certain dietary supplements, alcohol, and some foods markedly affect warfarin dose response. Therefore, there exists a need for a safer, more effective, and easily managed oral antithrombotic agent for the prevention of acute stroke in subjects with AF. This study was designed to evaluate the benefits and risks of study drug in subjects with AF.