In all three recently completed trials of novel anticoagulants vs warfarin (RE-LY, ROCKET-AF, and ARISTOTLE), the rate of intracranial hemorrhage (including both hemorrhagic stroke and other intracranial bleeds) was lower in patients assigned to the novel anticoag- ulant than in patients assigned to warfarin.84,85,87,88 2.1.7 General Approach to Recommendations About New Oral Anticoagulants in This Article: Our guideline panel elected to make recommendations only for those drugs that have received regulatory approval for use in AF (ie, dabigatran).89 Although based on the results of a single trial, there is evidence from RE-LY that dabigatran is no worse than VKA therapy with respect to nonfatal major extracranial bleeding and that it is similar or superior to warfarin with respect to nonfatal stroke, systemic embolism, and all-cause mortality in patients with nonvalvular AF (section 2.1.6). Therefore, for patients with non- rheumatic AF, wherever we recommend (or suggest) VKA therapy, we also recommend (or suggest) the use of dabigatran, and in these situations, our rec- ommendations simply refer to oral anticoagulation.88 We address the speci c question of whether to use Table 8 [Section 2.1.6] Phase 3 RCTs of New Oral Anticoagulants in Patients With AF Trial Intervention Comparator Status SPORTIF III Ximelagatran Warfarin (INR, 2.0-3.0) Published82,83 SPORTIF V RE-LY Dabigatran (150 or 110 mg bid) Warfarin (INR, 2.0-3.0) Published84 AVERROES Apixaban (5 mg bid) Aspirin (81-324 mg daily) Published86 ROCKET-AF Rivaroxaban (20 mg once daily) Warfarin (INR, 2.0-3.0) Published85 ARISTOTLE Apixaban (5 mg bid) Warfarin (INR, 2.0-3.0) Published87 ENGAGE-AF TIMI 48 Edoxaban (high- and low-dose regimens) Warfarin (INR, 2.0-3.0) Currently recruiting ARISTOTLE5Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation; AVERROES5Apixaban versus Acetylsalicylic Acid to Prevent Strokes; ENGAGE-AF TIMI 485Effective Anticoagulation With Factor xA Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction Study 48; INR5international normalized ratio; RE-LY5Randomized Evaluation of Long-Term Anticoagulation Therapy; ROCKET-AF5Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation; SPORTIF5Stroke Prevention Using an Oral Thrombin Inhibitor in Patients With AF. 