Abstract 18597: Systemic, Non-cerebral, Arterial Embolism in 21,105 Patients with Atrial Fibrillation Randomized to Edoxaban or Warfarin: Results from the ENGAGE AF-TIMI 48 Trial

Abstract

Background: Atrial fibrillation (AF) is widely recognized as a major risk factor for stroke and systemic embolism. Multiple trials comparing warfarin with factor specific oral anticoagulants have demonstrated that the newer agents are at least as effective as and generally safer than warfarin. However, none of these studies has provided a detailed analyses regarding systemic embolism, the less frequent component of the primary endpoint. Methods and Results: We did a prespecified analysis of data from the 21,105 patients with AF enrolled into ENGAGE AF-TIMI 48, a randomized trial comparing two once-daily regimens of edoxaban (high- and low-dose) with warfarin for the prevention of stroke and systemic embolism. Of the 1,016 patients who met the primary endpoint, 67 (6.6%) had a systemic embolic event (SEE) of which 13% were fatal. Risk factors for systemic embolism versus stroke include age (78 versus 74 years; P=0.005), permanent atrial fibrillation (72% versus 54%; P=0.009), and creatinine clearance ≤ 50 mL/min (42% versus 27%; P=0.01). Of the 73 total SEEs (includes multiple events), 62 involved the extremities (85%) and 30 required a surgical or percutaneous intervention (41%). In a meta-analysis of the four major trials comparing novel oral anticoagulants (NOACs) versus warfarin, the NOACs reduce the risk of SEE compared to warfarin (relative risk, 0.63; 95% confidence interval, 0.43 to 0.91; P=0.01), with less bleeding and a better safety profile. Conclusion: Although less frequent than stroke, systemic embolism results in significant morbidity and mortality in patients with AF. In a meta-analysis, NOACs reduce the risk of SEEs compared to warfarin.