title: Edoxaban vs. warfarin in vitamin K antagonist experienced and naive patients with atrial fibrillation†.
abstract: OBJECTIVE
  Edoxaban is an oral, once-daily factor Xa inhibitor that is non-inferior to well-managed warfarin in patients with atrial fibrillation (AF) for the prevention of stroke and systemic embolic events (SEEs). We examined the efficacy and safety of edoxaban vs. warfarin in patients who were vitamin K antagonist (VKA) naive or experienced.
  
  
  RESULTS
  ENGAGE AF-TIMI 48 randomized 21 105 patients with AF at moderate-to-high risk of stroke to once-daily edoxaban vs. warfarin. Subjects were followed for a median of 2.8 years. The primary efficacy endpoint was stroke or SEE. As a pre-specified subgroup, we analysed outcomes for those with or without prior VKA experience (>60 consecutive days). Higher-dose edoxaban significantly reduced the risk of stroke or SEE in patients who were VKA naive [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.56-0.90] and was similar to warfarin in the VKA experienced (HR 1.01, 95% CI 0.82-1.24; P interaction = 0.028). Lower-dose edoxaban was similar to warfarin for stroke or SEE prevention in patients who were VKA naive (HR 0.92, 95% CI 0.73-1.15), but was inferior to warfarin in those who were VKA experienced (HR 1.31, 95% 1.08-1.60; P interaction = 0.019). Both higher-dose and lower-dose edoxaban regimens significantly reduced the risk of major bleeding regardless of prior VKA experience (P interaction = 0.90 and 0.71, respectively).
  
  
  CONCLUSIONS
  In patients with AF, edoxaban appeared to demonstrate greater efficacy compared with warfarin in patients who were VKA naive than VKA experienced. Edoxaban significantly reduced major bleeding compared with warfarin regardless of prior VKA exposure.
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, 350 Longwood Avenue, 1st Floor, Boston, MA 02115, USA modonoghue@partners.org.
authors: Michelle L
authors: ML
authors: O'Donoghue
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, 350 Longwood Avenue, 1st Floor, Boston, MA 02115, USA.
authors: Christian T
authors: CT
authors: Ruff
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, 350 Longwood Avenue, 1st Floor, Boston, MA 02115, USA.
authors: Robert P
authors: RP
authors: Giugliano
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, 350 Longwood Avenue, 1st Floor, Boston, MA 02115, USA.
authors: Sabina A
authors: SA
authors: Murphy
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, 350 Longwood Avenue, 1st Floor, Boston, MA 02115, USA.
authors: Laura T
authors: LT
authors: Grip
authors: Daiichi Sankyo Pharma Development, Edison, NJ, USA.
authors: Michele F
authors: MF
authors: Mercuri
authors: Daiichi Sankyo, Inc., Parsippany, NJ, USA.
authors: Howard
authors: H
authors: Rutman
authors: Daiichi Sankyo Pharma Development, Edison, NJ, USA.
authors: Minggao
authors: M
authors: Shi
authors: Centrum Medyczne 'Ogrodowa', Skierniewice, Poland.
authors: Grzegorz
authors: G
authors: Kania
authors: Slany Municipal Hospital, Slany, Czech Republic.
authors: Ondrej
authors: O
authors: Cermak
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, 350 Longwood Avenue, 1st Floor, Boston, MA 02115, USA.
authors: Eugene
authors: E
authors: Braunwald
authors: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, 350 Longwood Avenue, 1st Floor, Boston, MA 02115, USA.
authors: Elliott M
authors: EM
authors: Antman
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications*; D004311:Double-Blind Method; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000627:therapeutic use*; D012307:Risk Factors; D020521:Stroke / 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: Atrial fibrillation; Edoxaban; Novel oral anticoagulant; Warfarin