The relative ef cacy and safety of NOACs were consistent across all patient subgroups with the exception that the relative reduction in major bleeding with NOACs was greater at centers with poor INR control as de ned as a center-based TTR < 66% (RR, 0.69; 95% CI, 0.59-0.81; P interaction .02). Lower dose NOAC regimens (dabigatran 110 mg and edoxaban 30/15 mg) showed similar overall reductions in stroke or systemic embolism but a more favorable bleeding pro le than warfarin but were associated with more ischemic strokes (the lower dose regimen edoxaban 30/15 mg is not approved for the stroke prevention indication). TABLE ] (Continued) Outcome Trial RE-LY ROCKET-AF ARISTOTLE ENGAGE AF-TIMI Dabigatran mg (n Dabigatran mg (n Warfarin (n Rivaroxaban mg (n Warfarin (n Apixaban mg (n Warfarin (n Edoxaban mg (n Edoxaban mg (n Warfarin (n HR CI) NA NA NA NA P < < NA NA < NA < < NA GI bleeding Event rate (%/y) HR CI) NA NA NA NA P NA < NA NA < NA ARISTOTLE Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; ENGAGE AF-TIMI Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation Thrombolysis In Myocardial Infarction study HR hazard ratio; RE-LY Randomized Evaluation of Long-Term Anticoagulation Therapy; ROCKET AF Rivaroxaban Once Daily Oral Direct Factor Xa Inhibi- tion Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation; SEE systemic embolic events. See Table legend for expansion of other abbreviations. NOACs vs Aspirin: Apixaban is the only NOAC that has been compared with aspirin in AF patients. 