title: Transition of patients from blinded study drug to open-label anticoagulation: the ENGAGE AF-TIMI 48 trial.
abstract: BACKGROUND
  At the end of 2 previous trials, an excess of stroke and bleeding was observed in patients with AF randomized to a new oral anticoagulant (NOAC) who transitioned to a vitamin K antagonist (VKA).
  
  
  OBJECTIVE
  The ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trial compared once-daily edoxaban to warfarin for stroke prevention in patients with AF. An end-of-trial transition plan was developed to minimize the risks of stroke due to inadequate anticoagulation and bleeding from excessive anticoagulation during this critical period.
  
  
  METHODS
  All patients on the blinded study drug at the trial's conclusion were included in this analysis. In pre-specified analyses, stroke, bleeding, and death that occurred through 30 days after the end-of-trial visit were stratified by randomized treatment allocation and open-label anticoagulant selected post-trial.
  
  
  RESULTS
  Of the 13,642 patients taking the blinded study drug at the end of the trial, 9,304 (68.2%) were transitioned to open-label VKA and 4,258 patients (31.2%) to an NOAC. There were 21 strokes evenly distributed across the 3 randomized treatment arms: warfarin 7 (1.90%/year), edoxaban high dose 7 (1.89%/year), edoxaban low dose 7 (1.85%/year). Major bleeding was also similar across the 3 treatment arms: warfarin 11 (2.98%/year), edoxaban high dose 10 (2.69%/year), edoxaban low dose 18 (4.76%/year). In patients transitioned to VKA, 85% of patients had at least 1 INR ≥ 2 by day 14 after the transition and 99% by day 30.
  
  
  CONCLUSIONS
  The ENGAGE AF-TIMI 48 transition plan protected patients from an excess of thrombotic and bleeding events and should be helpful in clinical practice when patients are transitioned between oral anticoagulants. (Global Study to Assess the Safety and Effectiveness of Edoxaban [DU-176b] vs Standard Practice of Dosing With Warfarin in Patients With Atrial Fibrillation [EngageAFTIMI48]; NCT00781391).
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: cruff@partners.org.
authors.forename: Christian T
authors.initials: CT
authors.lastname: Ruff
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.affiliation: Daiichi Sankyo Pharma Development, Edison, New Jersey.
authors.forename: Michele
authors.initials: M
authors.lastname: Mercuri
authors.affiliation: Daiichi Sankyo Pharma Development, Edison, New Jersey.
authors.forename: Valentin
authors.initials: V
authors.lastname: Curt
authors.affiliation: Quintiles, Inc., Research Triangle Park, North Carolina.
authors.forename: Joshua
authors.initials: J
authors.lastname: Betcher
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Laura
authors.initials: L
authors.lastname: Grip
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Abby L
authors.initials: AL
authors.lastname: Cange
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Crompton
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Naveen
authors.initials: N
authors.lastname: Deenadayalu
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Antman
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D004311:Double-Blind Method; D057915:Drug Substitution / Q000379:methods*; D015951:Factor Xa / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D011725:Pyridines / Q000008:administration & dosage; D013844:Thiazoles / Q000008:administration & dosage; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage
chemical_list: D000925:Anticoagulants; D011725:Pyridines; D013844:Thiazoles; D014859:Warfarin; D015951:Factor Xa; C552171:edoxaban
keywords: anticoagulation; atrial fibrillation; edoxaban; factor Xa inhibitor; new oral anticoagulants; vitamin K antagonist