Balancing the benefits and risks of 2 doses of dabigatran compared with warfarin in atrial fibrillation

J Am Coll Cardiol. 2013 Sep 3;62(10):900-8. doi: 10.1016/j.jacc.2013.05.042. Epub 2013 Jun 13.

Abstract

Objectives: 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).

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Antithrombins / administration & dosage*
  • Antithrombins / adverse effects
  • Antithrombins / therapeutic use
  • Atrial Fibrillation / drug therapy*
  • Benzimidazoles / administration & dosage*
  • Benzimidazoles / adverse effects
  • Benzimidazoles / therapeutic use
  • Dabigatran
  • Female
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Humans
  • Male
  • Risk Factors
  • Stroke / drug therapy
  • Stroke / epidemiology
  • Stroke / prevention & control*
  • Treatment Outcome
  • Warfarin / administration & dosage*
  • Warfarin / adverse effects
  • Warfarin / therapeutic use
  • beta-Alanine / administration & dosage
  • beta-Alanine / adverse effects
  • beta-Alanine / analogs & derivatives*
  • beta-Alanine / therapeutic use

Substances

  • Anticoagulants
  • Antithrombins
  • Benzimidazoles
  • beta-Alanine
  • Warfarin
  • Dabigatran

Associated data

  • ClinicalTrials.gov/NCT00262600