Dabigatran versus warfarin: effects on ischemic and hemorrhagic strokes and bleeding in Asians and non-Asians with atrial fibrillation

Stroke. 2013 Jul;44(7):1891-6. doi: 10.1161/STROKEAHA.113.000990. Epub 2013 Jun 6.

Abstract

Background and purpose: Intracranial hemorrhage rates are higher in Asians than non-Asians, especially in patients receiving warfarin. This randomized evaluation of long-term anticoagulation therapy subgroup analysis assessed dabigatran etexilate (DE) and warfarin effects on stroke and bleeding rates in patients from Asian and non-Asian countries.

Methods: There were 2782 patients (15%) from 10 Asian countries and 15 331 patients from 34 non-Asian countries. A Cox regression model, with terms for treatment, region, and their interaction was used.

Results: Rates of stroke or systemic embolism in Asians were 3.06% per year on warfarin, 2.50% per year on DE 110 mg BID (DE 110), and 1.39% per year on DE 150 mg BID (DE 150); in non-Asians, the rates were 1.48%, 1.37%, and 1.06% per year with no significant treatment-by-region interactions. Hemorrhagic stroke on warfarin occurred more often in Asians than non-Asians (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.3-4.7; P=0.007), with significant reductions for DE compared with warfarin in both Asian (DE 110 versus warfarin HR, 0.15; 95% CI, 0.03-0.66 and DE 150 versus warfarin HR, 0.22; 95% CI, 0.06-0.77) and non-Asian (DE 110 versus warfarin HR, 0.37; 95% CI, 0.19-0.72 and DE 150 versus warfarin HR, 0.28; 95% CI, 0.13-0.58) patients. Major bleeding rates in Asians were significantly lower on DE (both doses) than warfarin (warfarin 3.82% per year, DE 110 2.22% per year, and DE 150 2.17% per year).

Conclusions: Hemorrhagic stroke rates were higher on warfarin in Asians versus non-Asians, despite similar blood pressure, younger age, and lower international normalized ratio values. Hemorrhagic strokes were significantly reduced by DE in both Asians and non-Asians. DE benefits were consistent across Asian and non-Asian subgroups.

Clinical trial registration url: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

Keywords: Asia; RE-LY; atrial fibrillation; bleeding; dabigatran; intracranial hemorrhage; warfarin.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects*
  • Antithrombins / administration & dosage
  • Antithrombins / adverse effects
  • Asia / epidemiology
  • Asia / ethnology
  • Asian People / ethnology
  • Atrial Fibrillation / drug therapy*
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / adverse effects*
  • Brain Ischemia / epidemiology
  • Brain Ischemia / etiology
  • Dabigatran
  • Female
  • Humans
  • Intracranial Hemorrhages / epidemiology
  • Intracranial Hemorrhages / etiology*
  • Male
  • Middle Aged
  • Pyridines / administration & dosage
  • Pyridines / adverse effects*
  • Stroke / epidemiology
  • Stroke / etiology*
  • Warfarin / administration & dosage
  • Warfarin / adverse effects*

Substances

  • Anticoagulants
  • Antithrombins
  • Benzimidazoles
  • Pyridines
  • Warfarin
  • Dabigatran

Associated data

  • ClinicalTrials.gov/NCT00262600