5719Edoxaban versus warfarin in patients with atrial fibrillation in relation to stroke risk. A subanalysis of the ENGAGE AF-TIMI 48 study

Abstract

Introduction: The CHA2DS2VASc score assesses stroke risk more accurately than the CHADS2 score. The differential efficacy and safety of the direct factor Xa inhibitor edoxaban compared to well managed warfarin on stroke risk, as assessed by the CHA2DS2VASc score, has not been established. Purpose: To investigate the differential efficacy and safety of edoxaban versus well managed warfarin in relation to CHA2DS2VASc score. Methods: The ENGAGE‐AF TIMI 48 trial randomized 21,105 patients with nonvalvular atrial fibrillation to once‐daily warfarin, higher dose edoxaban regimen (HDER, 60/30 mg) or lower dose edoxaban regimen (LDER, 30/15 mg). For the current subanalysis, patients were grouped based on CHA2DS2VASc score (≤2, 3, 4, 5, ≥6). Efficacy (stroke or systemic embolism [SSE]), safety (major bleeding [MB]), intracranial hemorrhage and cardiovascular hospitalizations were compared for HDER and warfarin in each group, since the LDER is not approved for use. Results: Incremental risks of SSE (from 0.55 to 2.99%/yr) and MB (from 1.80 to 4.88%/year) in the warfarin group were seen with increasing CHA2DS2VASc score. No significant effect modification by CHA2DS2VASc score was seen for SSE (p‐int=0.546) or MB (p‐int=0.99) with HDER vs warfarin (Figure). Intracranial hemorrhage and hospitalization of cardiovascular causes were also reduced with HDER in all groups except CHA2DS2VASc<2. Because event rates were higher as the CHA2DS2VASc increased, the number of events prevented with HDER tended to be greater at higher scores. Conclusion: The benefit of edoxaban over warfarin in the prevention of stroke or systemic embolism is maintained among different strata of stroke risk. While remaining similarly effective, edoxaban provides an incremental absolute reduction in safety events over warfarin with increasing CHA2DS2VASc scores. (Figure Presented).