title: Edoxaban vs. Warfarin in East Asian Patients With Atrial Fibrillation　- An ENGAGE AF-TIMI 48 Subanalysis.
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.
  
  
  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.
authors.affiliation: The Cardiovascular Institute.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamashita
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Koretsune
authors.forename: Yuejin
authors.initials: Y
authors.lastname: Yang
authors.forename: Shih-Ann
authors.initials: SA
authors.lastname: Chen
authors.forename: Namsik
authors.initials: N
authors.lastname: Chung
authors.forename: Yuichi J
authors.initials: YJ
authors.lastname: Shimada
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimura
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Abe
authors.forename: Michele
authors.initials: M
authors.lastname: Mercuri
authors.forename: Christian T
authors.initials: CT
authors.lastname: Ruff
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000453:epidemiology; D004311:Double-Blind Method; D004617:Embolism / Q000453:epidemiology / Q000517:prevention & control*; D005202:Asia, Eastern / Q000453:epidemiology; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control*; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D011725:Pyridines; D013844:Thiazoles; D014859:Warfarin; C552171:edoxaban