title: Valvular Heart Disease Patients on Edoxaban or Warfarin in the ENGAGE AF-TIMI 48 Trial.
abstract: BACKGROUND
  The use of non-vitamin K antagonist oral anticoagulants (NOACs) instead of vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and coexisting valvular heart disease (VHD) is of substantial interest.
  
  
  OBJECTIVE
  This study explored outcomes in patients with AF with and without VHD in the ENGAGE AF-TIMI 48 (Effective Anticoagulation with factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction 48) trial, comparing edoxaban with warfarin.
  
  
  METHODS
  Valvular heart disease was defined as history or baseline echocardiography evidence of at least moderate aortic/mitral regurgitation, aortic stenosis, or prior valve surgery (bioprosthesis replacement, valve repair, valvuloplasty). Patients with moderate to severe mitral stenosis or mechanical heart valves were excluded from the trial. Comparisons were made of rates of stroke/systemic embolic event (SSEE), major bleeding, additional efficacy and safety outcomes, as well as net clinical outcomes, in patients with or without VHD treated with edoxaban or warfarin, using adjusted Cox proportional hazards.
  
  
  RESULTS
  After adjustment for multiple baseline characteristics, compared with no-VHD patients (n = 18,222), VHD patients (n = 2,824) had a similar rate of SSEE but higher rates of death (hazard ratio [HR]: 1.40; 95% confidence interval [CI]:1.26 to 1.56; p <0.001), major adverse cardiovascular events (HR: 1.29; 95% CI: 1.16 to 1.43; p <0.001), and major bleeding (HR: 1.21; 95% CI: 1.03 to 1.42; p = 0.02). Higher-dose edoxaban regimen had efficacy similar to warfarin in the presence of VHD (for SSEE, HR: 0.69; 95% CI: 0.44 to 1.07, in patients with VHD, and HR: 0.91; 95% CI: 0.77 to 1.07, in patients without VHD; p interaction [pint] = 0.26; and for less major bleeding, HR: 0.74; 95% CI: 0.53 to 1.02 in patients with VHD, and HR: 0.82; 95% CI: 0.71 to 0.94, in patients with no VHD; pint= 0.57).
  
  
  CONCLUSIONS
  The presence of VHD increased the risk of death, major adverse cardiovascular events, and major bleeding but did not affect the relative efficacy or safety of higher-dose edoxaban versus warfarin in AF. (Global Study to Assess the Safety and Effectiveness of Edoxaban (DU-176b) vs. Standard Practice of Dosing With Warfarin in Patients With Atrial Fibrillation [ENGAGE AF-TIMI 48]; NCT00781391).
authors.affiliation: Institute of Cardiology and Center of Excellence on Aging, G. d'Annunzio University, Chieti, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
authors.affiliation: Institute of Cardiology and Center of Excellence on Aging, G. d'Annunzio University, Chieti, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Renda
authors.affiliation: Cardiovascular Medicine Division, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Carnicelli
authors.affiliation: Cardiovascular Medicine Division, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Francesco
authors.initials: F
authors.lastname: Nordio
authors.affiliation: Cardiovascular Medicine Division, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Marco
authors.initials: M
authors.lastname: Trevisan
authors.affiliation: Pharma Development, Daiichi-Sankyo, Parsippany, New Jersey.
authors.forename: Michele F
authors.initials: MF
authors.lastname: Mercuri
authors.affiliation: Cardiovascular Medicine Division, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Christian T
authors.initials: CT
authors.lastname: Ruff
authors.affiliation: Cardiovascular Medicine Division, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Antman
authors.affiliation: Cardiovascular Medicine Division, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.affiliation: Cardiovascular Medicine Division, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: rgiugliano@partners.org.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications*; D004311:Double-Blind Method; D004617:Embolism / Q000517:prevention & control*; D005260:Female; D006349:Heart Valve Diseases / Q000150:complications*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000627:therapeutic use; D020521:Stroke / Q000517:prevention & control*; D013844:Thiazoles / Q000627:therapeutic use; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D011725:Pyridines; D013844:Thiazoles; D014859:Warfarin; C552171:edoxaban
keywords: NOACs; anticoagulation; atrial fibrillation; edoxaban; valvular heart disease; warfarin