Abstract-Vitamin K antagonists have been the standard in stroke prophylaxis in patients with atrial fibrillation for decades, but several limitations make it difficult for patients to tolerate chronic anticoagulation treatment. New drugs are under evaluation in clinical trials, including direct thrombin inhibitors and factor Xa inhibitors. Antiplatelet agents such as clopidogrel and aspirin are alternatives to warfarin for stroke prevention but have proven less efficacious in trials. The only drug to have completed a Phase III trial successfully thus far is dabigatran. The 150-mg twice-a-day dose was superior to warfarin in efficacy and similar for major bleeding, whereas the 110-mg twice-a-day dose was noninferior for efficacy and reduced major bleeding. Both doses reduced intracranial hemorrhages substantially compared with warfarin. Dabigatran-assigned patients had a higher incidence of discontinuation due to gastrointestinal symptoms. Clinically apparent myocardial infarction rates were slightly higher in the dabigatran groups than the warfarin group. Dabigatran is the first agent to show superiority over warfarin for stroke prevention in atrial fibrillation, raising the standard for newer agents. (Stroke. 2010;41[suppl 1]:S17-S20.)Key Words: anticoagulation Ⅲ atrial fibrillation Ⅲ prevention A trial fibrillation is the most common cardiac arrhythmia with a projected incidence of 5.6 to 15.9 million people by the year 2050. 1,2 The incidence increases with patient age. 3 There is an increased risk of stroke 4 ; thus, adequate anticoagulation using warfarin is the cornerstone of therapy. In the next few years, the role of warfarin as the anticoagulant of choice is likely to be challenged as novel agents are developed (Figure 1). Vitamin K AntagonistsCurrently, the vitamin K antagonist warfarin is the only oral anticoagulant licensed for long-term use in patients with atrial fibrillation. Despite the effectiveness of vitamin K antagonists, they are limited by factors such as drug-drug interactions, food interactions, slow onset of action, hemorrhage, and routine anticoagulation monitoring to maintain a therapeutic international normalized ratio (INR). 5 These limitations have resulted in the underuse of warfarin, 6 leaving many at risk. New oral anticoagulants are needed that eliminate the problems of warfarin use at the same time as remaining effective for stroke prevention.In a recent Phase IIA trial, the new vitamin K antagonist tecarfarin was evaluated in 66 individuals with atrial fibrillation at mild-to-moderate risk of stroke. 7 It is not metabolized by the hepatic cytochrome P450 system and has fewer interactions than warfarin, theoretically making it easier to control. There is much evidence that patients who spend more time in the therapeutic INR range of 2.0 to 3.0 exhibit fewer clinical events. 8 -10 The hypothesis of the study was that the time in the therapeutic INR range on tecarfarin would exceed that on warfarin. Sixty-four patients were taking warfarin and switched to tecarfarin. Excluding t...