Physicians' Academy for Cardiovascular Education

Efficacy and safety of DOAC versus warfarin consistent across CHA2DS2-VASc scores

Edoxaban versus warfarin in patients with atrial fibrillation in relation to the risk of stroke: A secondary analysis of the ENGAGE AF-TIMI 48 study

Literature - De Groot JR, Ruff CT, Murphy SA et al., - Am Heart J. 2021 Jan 22;235:132-139. doi: 10.1016/j.ahj.2021.01.013.

Introduction and methods

The ENGAGE AF-TIMI 48 trial has shown that oral factor Xa inhibitor edoxaban is noninferior to well-managed warfarin in the prevention of stroke or systemic embolism (SEE) in patients with AF [1,2]. The risk of stroke and major bleeding varies between patients. The CHA2DS2-VASc score can predict this risk in patients with AF on anticoagulation [3]. This analysis investigated the efficacy and safety of edoxaban versus warfarin across CHA2DS2-VASc scores in the ENGAGE AF-TIMI 48 trial.

ENGAGE AF-TIMI 48 was a phase 3, multinational, double-blind, double-dummy, randomized trial in 21 105 patients with AF and CHADS2 scores ≥2. Patients were randomized to edoxaban 60 mg, edoxaban 30 mg or warfarin. The edoxaban dose was reduced by 50% in patients with weight ≤60 kg, creatinine clearance ≤50 mL/min, or when they used strong P-glycoprotein inhibitors. The primary efficacy endpoint was SSE and the principal safety endpoint was major bleeding. Median follow-up was 2.8 years. This analysis compared the approved edoxaban dose (60/30 mg) to warfarin in patients stratified according to CHA2DS2-VASc score: ≤3 (n=4159, 29.6%), 4 (n=4066, 28.9%), 5 (n=3165, 22.5%, and ≥6 (n=2681, 19.1%).

Main results


The efficacy and safety profile of edoxaban versus warfarin was consistent across the spectrum of CHA2DS2-VASc scores. Stroke, embolic events, bleeding and CV mortality rates increased with increasing CHA2DS2-VASc score. While relative risk reductions remained similar, the absolute number of prevented events was greater with edoxaban as compared to warfarin in patients with higher CHA2DS2-VASc scores.


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Find this article online at Am Heart J.

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