title: Efficacy and safety of edoxaban compared with warfarin in patients with atrial fibrillation and heart failure: insights from ENGAGE AF-TIMI 48.
abstract: In the ENGAGE AF-TIMI 48 trial, edoxaban, a factor Xa inhibitor, was not found to be inferior to warfarin for the prevention of stroke or systemic embolic events (SEE) in patients with atrial fibrillation (AF) and was associated with significantly less bleeding. The higher-dose edoxaban regimen (HDER; 60 mg dose-reduced to 30 mg once daily) has been approved in various countries in Europe, the USA, and Japan. Among patients treated with vitamin K antagonists (VKAs), symptomatic heart failure (HF) is an independent risk factor for lower time-in-therapeutic range, which reduces the efficacy and safety of VKA therapy. We evaluated the efficacy and safety of edoxaban compared with warfarin across the spectrum of HF severity in the ENGAGE AF-TIMI 48 trial.
  
  
  
  Of 14 071 patients randomized to well-controlled warfarin or the HDER, 5926 (42%) had no history of HF, 6344 (45%) were in New York Heart Association (NYHA) class I-II, and 1801 (13%) were in NYHA class III-IV. The efficacy of edoxaban compared with warfarin in preventing stroke/SEE was similar in patients without and with HF regardless of the severity of HF; [HDER vs. warfarin: No-HF: hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.69-1.11; NYHA class I-II: HR 0.88, 95% CI 0.69-1.12; NYHA class III-IV: HR 0.83, 95% CI 0.55-1.25; Pinteraction = 0.97]. Compared with warfarin, HDER was consistently associated with lower risk of major bleeding (No-HF: HR 0.82, 95% CI 0.68-0.99; NYHA class I-II: HR 0.79, 95% CI 0.65-0.96; NYHA class III-IV: HR 0.79, 95% CI 0.54-1.17; Pinteraction = 0.96).
  
  
  
  The relative efficacy and safety of HDER compared with well-managed warfarin in AF patients with HF were similar to those without HF.
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, Boston, MA, 02115, USA.
authors.forename: Giulia
authors.initials: G
authors.lastname: Magnani
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, Boston, MA, 02115, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, Boston, MA, 02115, USA.
authors.forename: Christian T
authors.initials: CT
authors.lastname: Ruff
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, Boston, MA, 02115, USA.
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, Boston, MA, 02115, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Nordio
authors.affiliation: University of Brescia, Brescia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.affiliation: Fondazione Cardiocentro Ticino, Lugano, Switzerland.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Moccetti
authors.affiliation: Kerckhoff-Klinik, Bad Nauheim, Germany.
authors.forename: Veselin
authors.initials: V
authors.lastname: Mitrovic
authors.affiliation: Daiichi Sankyo, Parsippany, NJ, USA.
authors.forename: Minggao
authors.initials: M
authors.lastname: Shi
authors.affiliation: Daiichi Sankyo, Edison, NJ, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Mercuri
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, Boston, MA, 02115, USA.
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Antman
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 350 Longwood Avenue, Boston, MA, 02115, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000150:complications*; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011725:Pyridines / Q000627:therapeutic use*; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011725:Pyridines; D013844:Thiazoles; D014859:Warfarin; C552171:edoxaban
keywords: Anticoagulation management; Atrial fibrillation; Edoxaban; Heart failure; New oral anticoagulants; Thromboembolic risk prevention