The predictable anticoagulant effects of the NOACs enable their administration in xed doses without the need for routine coagulation monitoring, thereby simplifying therapy. Individually in their respective phase 3 trials (Table 4), dabigatran, rivaroxaban, apixaban, and edoxaban have been shown to be at least as safe and effective as warfarin for preventing stroke and systemic embolism in patients A meta-analysis of the four phase 3 trials compared patients taking NOACs (higher dose) (n 42,411) with warfarin (n 29,272) (e-Table 15).124 NOACs signi cantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR, 0.81; 95% CI, 0.73- 0.91; P < .0001). The bene t was driven primarily by a 51% reduction in hemorrhagic stroke (RR, 0.49; 95% CI, 0.38-0.64; P < .0001). Ischemic stroke was similar between NOACs and warfarin (RR, 0.92; 95% CI, 0.83- 1.02; P .10). NOACs were also associated with a signi cant 10% reduction in all-cause mortality (RR, safety, NOACs were associated with a nonsigni cant 14% reduction in major bleeding (RR, 0.86; 95% CI, 0.73-1.00; P .06) but a substantial 52% reduction in ICH (RR, 0.48; 95% CI, 0.39-0.59; P < .0001). NOACs were, however, associated with a signi cant increase in P .04). 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). 