title: Long-term evaluation of dabigatran 150 vs. 110 mg twice a day in patients with non-valvular atrial fibrillation.
abstract: OBJECTIVE
  The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial allowed patients who completed the trial receiving their assigned dabigatran 150 mg (D150) or 110 mg (D110) twice a day to continue into the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial. This permitted assessment of outcomes over a median of 4.6 and a maximum of 6.7 years, respectively.
  
  
  RESULTS
  The analysed population included only those patients who completed RE-LY on dabigatran and continued into RELY-ABLE without interruption of assigned dabigatran. Cumulative risk was expressed as Kaplan-Meier plots. Outcomes were compared using Cox proportional hazard modelling. Stroke or systemic embolization rates were 1.25 and 1.54% per year (D150 and D110, respectively); hazard ratio (HR) 0.81 [95% confidence interval (CI): 0.68-0.96] (P = 0.02). Ischaemic stroke was 1.03 (D150) and 1.29%/year (D110); HR 0.79 (95% CI: 0.66-0.95) (P = 0.01). Haemorrhagic stroke rates were 0.11 (D150) and 0.13%/year (D110); HR 0.91 (95% CI: 0.51-1.62) (P = 0.75). Rates of major haemorrhage were 3.34 (D150) and 2.76%/year (D110); HR 1.22 (95% CI: 1.08-1.37) (P = 0.0008). Intracranial haemorrhage rates were 0.32 (D150) and 0.23%/year (D110); HR 1.37 (95% CI: 0.93-2.01) (P = 0.11). Mortality was 3.43 (D150) and 3.55%/year (D110); HR 0.97 (95% CI: 0.87-1.08) (P = 0.54).
  
  
  CONCLUSIONS
  Annualized rates of all outcomes were constant with better efficacy of D150, less major bleeding with D110, and low intracerebral haemorrhage rates for both doses. There were no additional safety concerns. This is the longest continuous randomized experience of a novel anticoagulant.
authors.affiliation: Sidney Kimmel Medical College, Thomas Jefferson University, 1999 Sproul Rd., Broomall, Philadelphia, PA, USA Lankenau Medical Center, Wynnewood, PA, USA michael.ezekowitz@comcast.net.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Ezekowitz
authors.affiliation: Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Eikelboom
authors.affiliation: Department of Medical Sciences, Uppsala Clinical Research Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Oldgren
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Reilly
authors.affiliation: Boehringer Ingelheim GmbH & Co. KG, Ingelheim, Germany Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Brueckmann
authors.affiliation: Sidney Kimmel Medical College, Thomas Jefferson University, 1999 Sproul Rd., Broomall, Philadelphia, PA, USA.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Kent
authors.affiliation: Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada.
authors.forename: Janice
authors.initials: J
authors.lastname: Pogue
authors.affiliation: Lankenau Institute for Medical Research, Wynnewood, PA, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Spahr
authors.affiliation: Boehringer Ingelheim GmbH & Co. KG, Ingelheim, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Clemens
authors.affiliation: Boehringer Ingelheim GmbH & Co. KG, Ingelheim, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Noack
authors.affiliation: Department of Neurology, University Hospital Essen, Essen, Germany.
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Diener
authors.affiliation: Department of Medical Sciences, Uppsala Clinical Research Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.affiliation: Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada.
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.affiliation: Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Connolly
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use; D000991:Antithrombins / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality; D000069604:Dabigatran / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D020300:Intracranial Hemorrhages / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D020521:Stroke / Q000453:epidemiology; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D014859:Warfarin; D000069604:Dabigatran
keywords: Atrial fibrillation; Dabigatran etexilate; Long-term outcome; Stroke