The Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE-A) trial, which also predated the investigation of NOACs, compared aspirin plus clopidogrel vs aspirin monotherapy among patients in whom VKA was The study found a decrease in risk of stroke with dual antiplatelet therapy (DAPT), but the major bleeding rates with aspirin-clopidogrel were comparable to rates seen with warfarin (approximately 2% per year). 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. 