Abstract 17211: Edoxaban versus Warfarin in Patients With Atrial Fibrillation in the US FDA Approval Population: An Analysis From the ENGAGE AF-TIMI 48 Trial
Background: Edoxaban (edo), a QD oral direct factor Xa inhibitor, is non-inferior to warfarin for preventing stroke or systemic embolism (SE) in mod-high risk pts with AF. Due to reduced protection from ischemic stroke in pts with CrCl >95 ml/min, the US FDA approved the higher dose edo regimen in pts with AF and a CrCl 15-95 ml/min (60mg QD if CrCl 50-95 ml/min; 30mg QD if CrCl 15-50 ml/min) without dose reduction for weight <60 kg or use of P-glycoprotein (P-gp) inhibitors. We report here for the first time the clinical characteristics, efficacy and safety of the FDA-approved population.
Methods: From the ENGAGE AF-TIMI 48 trial population, we excluded pts who received the lower-dose edo regimen (30/15 mg), had CrCl >95 ml/min, or were dose-reduced for weight≤ 60 kg or potent P-gp use. The 1° efficacy endpoint was stroke/SE and principal safety endpoint was major bleeding. Efficacy data are from the ITT cohort in the overall study period, unless otherwise specified.
Results: There were 9387 pts with CrCl 15-95 ml/min randomized to either warfarin or edo 60/30 mg per the FDA label followed for 2.8 yrs (median). These pts were older (74 vs 64 yrs), more likely women (40 vs 33%), and had higher CHADS2 and HAS-BLED scores compared to pts not included in the FDA label, but were balanced by randomization group. The annualized rate of stroke/SE on-treatment was 1.11% with edo vs. 1.72% with warfarin (HR vs. warfarin 0.64 [0.51-0.81], p<0.001). Rates in the ITT cohort were 1.63% and 2.02% with edo and warfarin, respectively (HR 0.81 [0.67-0.97], p=0.023). Ischemic stroke rates were similar (1.31 vs 1.39%, HR 0.94, p=0.97). Edo significantly reduced hemorrhagic stroke, CV death, major and intracranial bleeding events (Fig).
Conclusion: Among high risk pts in the ENGAGE AF-TIMI 48 trial who represent the FDA approval population and dosing regimen of edo, treatment with edo 60/30 mg is superior to warfarin in the prevention of stroke/SE and reduces major bleeding, intracranial hemorrhage, and CV death.
Author Disclosures: A. Eisen: None. R.P. Giugliano: Honoraria; Modest; Merck. Consultant/Advisory Board; Modest; Amgen, GlaxoSmithKline, Merck, Portola, American College of Cardiology, CVS Caremark. Other; Modest; St Jude Medical. Research Grant; Significant; Amgen, Merck. Other; Significant; Lexicon. C.T. Ruff: Research Grant; Modest; Astra Zeneca, Eisai, Intarcia. Research Grant; Significant; Daiichi-Sankyo. Consultant/Advisory Board; Modest; Boehringer Ingelheim, Bayer, Portola.. Consultant/Advisory Board; Significant; Daiichi Sankyo.. F. Nordio: None. H.S. Gogia: Research Grant; Modest; Daiichi-Sankyo. V.R. Awasty: Research Grant; Modest; Daiichi-Sankyo. D.A. Henderson: Research Grant; Modest; Daiichi-Sankyo. M. Mercuri: Employment; Significant; Daiichi-Sankyo. H. Rutman: Employment; Significant; Daiichi-Sankyo. E.M. Antman: None. E. Braunwald: Research Grant; Significant; Grant support to institution from Daiichi Sankyo.
- © 2015 by American Heart Association, Inc.