title: Balancing the benefits and risks of 2 doses of dabigatran compared with warfarin in atrial fibrillation.
abstract: OBJECTIVE
  This study sought to compare the net clinical benefit of dabigatran 110 mg bid and 150 mg bid with that of warfarin in patients with atrial fibrillation (AF).
  
  
  BACKGROUND
  In patients with AF, dabigatran 110 mg bid and 150 mg bid are associated with similar rates of death. However, the higher dose reduces ischemic stroke and increases bleeding compared with the lower dose. Therefore, there is uncertainty about how to evaluate the overall benefit of the 2 doses.
  
  
  METHODS
  In 18,113 AF patients in the RE-LY (Randomized Evaluation of Long Term Anticoagulant Therapy) trial, we used a previously developed method for integrating ischemic and bleeding events as "ischemic stroke equivalents" in order to compare a weighted benefit of 2 doses of dabigatran with each other, and with that of warfarin.
  
  
  RESULTS
  Compared with warfarin, there was a significant decrease in ischemic stroke equivalents with both dabigatran doses: -0.92 per 100 patient years (95% confidence interval [CI]: -1.74 to -0.21, p = 0.02) with dabigatran 110 mg bid and -1.08 (95% CI: -1.86 to -0.34, p = 0.01) with dabigatran 150 mg bid. There was no significant difference in ischemic stroke equivalents between the 2 doses: -0.16 (95% CI: -0.80 to 0.43) comparing dabigatran 150 mg bid with 110 bid. When including death in the weighted benefit calculations, the results were similar.
  
  
  CONCLUSIONS
  On a group level both doses of dabigatran as compared with warfarin have similar benefits when considering a weighted estimate including both efficacy and safety. The similar overall benefits of the 2 doses of dabigatran versus warfarin support individualizing the dose based on patient characteristics and physician and patient preferences. (Randomized Evaluation of Long Term Anticoagulant Therapy [RE-LY] With Dabigatran Etexilate; NCT00262600).
authors.affiliation: Population Health Research Institute, McMaster University, 237 Barton St. East, Hamilton, Ontario, Canada. eikelbj@mcmaster.ca
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Connolly
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hart
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.forename: Paul
authors.initials: P
authors.lastname: Reilly
authors.forename: Jonas
authors.initials: J
authors.lastname: Oldgren
authors.forename: Sean
authors.initials: S
authors.lastname: Yang
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000991:Antithrombins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000069604:Dabigatran; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008297:Male; D012307:Risk Factors; D020521:Stroke / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control*; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015091:beta-Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D015091:beta-Alanine; D014859:Warfarin; D000069604:Dabigatran
keywords: AF; CI; CNS; FDA; Food and Drug Administration; MI; TIA; atrial fibrillation; central nervous system; confidence interval; dabigatran; myocardial infarction; net benefit; transient ischemic attack; warfarin