VKAs Compared With APT: Of 12 studies comparing warfarin vs APT, warfarin was associated with a 39% relative risk reduction (95% CI, 22-52) in strokes In the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE W), the largest of these studies, warfarin was superior to DAPT to warfarin for stroke and a TABLE 4 ] Phase 3 AF Trials of NOAC vs Warfarin: Summary of Key Ef cacy and Safety Results Outcome Trial ENGAGE AF-TIMI 4876 Dabigatran (n 6,076) Dabigatran (n 6,015) Warfarin (n Rivaroxaban (n 7,131) Warfarin (n Apixaban (n 9,120) Warfarin (n Edoxaban (n 7,035) Edoxaban (n 7,034) Warfarin (n 7,036) Ef cacy Stroke/SEE Event rate (%/y) Ischemic stroke Event rate (%/y) Hemorrhagic stroke Event rate (%/y) P < .001 < .001 NA .02 NA < .001 NA < .001 < .001 NA MI Event rate (%/y) All-cause death Event rate (%/y) Safety Major bleeding Event rate (%/y) ICH Event rate (%/y) (Continued) Evidence-Based Medicine [ # C H E S T N O V E M B E R ] cardiovascular composite outcome, with similar rates of NOACs Compared With VKAs: Several NOACs that directly inhibit thrombin (factor IIa) or activated factor X (factor Xa) have been approved as alternatives to VKAs for stroke prevention in AF. They differ from VKAs in that they have a rapid onset/offset of action, absence of an effect of dietary vitamin K intake on their activity, and fewer drug interactions. The predictable anticoagulant effects of the NOACs enable their administration in xed doses without the need for routine coagulation monitoring, thereby simplifying therapy. 