Edoxaban vs. Warfarin in East Asian Patients With Atrial Fibrillation - An ENGAGE AF-TIMI 48 Subanalysis

Circ J. 2016;80(4):860-9. doi: 10.1253/circj.CJ-15-1082. Epub 2016 Feb 16.

Abstract

Background: In the multinational, double-blind, double-dummy ENGAGE AF-TIMI 48 phase 3 study, once-daily edoxaban was non-inferior to warfarin for prevention of stroke or systemic embolism event (SEE) in patients with non-valvular atrial fibrillation (AF). Here, we evaluated the efficacy and safety of edoxaban in patients from East Asia.

Methods and results: Patients aged ≥21 years with documented AF and CHADS score ≥2 were randomized to receive once-daily edoxaban higher-dose (60 mg) or lower-dose (30 mg) regimen or warfarin dose-adjusted to an international normalized ratio of 2.0-3.0. Patients with a creatinine clearance of 30-50 ml/min, weighing ≤60 kg, or receiving strong p-glycoprotein inhibitors at randomization or during the study received a 50% dose reduction of edoxaban or matched placebo. This prespecified subanalysis included 1,943 patients from Japan, China, Taiwan, and South Korea. The annualized rate of stroke/SEE for higher-dose edoxaban was 1.34% vs. 2.62% for warfarin (hazard ratio [HR], 0.53; 95% confidence interval [CI]: 0.31-0.90, P=0.02) and 2.52% for lower-dose edoxaban (HR, 0.98; 95% CI: 0.63-1.54, P=0.93). Compared with warfarin (4.80%), major bleeding was significantly reduced for the higher-dose (2.86%; HR, 0.61; 95% CI: 0.41-0.89, P=0.011) and lower-dose regimens (1.59%; HR, 0.34; 95% CI: 0.21-0.54, P<0.001).

Conclusions: Once-daily edoxaban provided similar efficacy to warfarin while reducing major bleeding risk in the East Asian population.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / epidemiology
  • Double-Blind Method
  • Embolism / epidemiology
  • Embolism / prevention & control*
  • Far East / epidemiology
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Humans
  • Pyridines / administration & dosage*
  • Pyridines / adverse effects
  • Stroke / epidemiology
  • Stroke / prevention & control*
  • Thiazoles / administration & dosage*
  • Thiazoles / adverse effects
  • Warfarin / administration & dosage*
  • Warfarin / adverse effects

Substances

  • Pyridines
  • Thiazoles
  • Warfarin
  • edoxaban