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

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.

• Authors: Masatsugu Hori, Stuart J Connolly, Jun Zhu, Li Sheng Liu, Chu-Pak Lau, Prem Pais, Denis Xavier, Sung Soon Kim, Razali Omar, Antonio L Dans, Ru San Tan, Jyh-Hong Chen, Supachai Tanomsup, Mitsunori Watanabe, Masahide Koyanagi, Michael D Ezekowitz, Paul A Reilly, Lars Wallentin, Salim Yusuf, RE-LY Investigators
• Journal: Stroke (Stroke) Vol. 44 Issue 7 Pg. 1891-6 (Jul 2013) ISSN: 1524-4628 [Electronic] United States
• PMID: 23743976 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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