Dabigatran and warfarin in vitamin K antagonist-naive and -experienced cohorts with atrial fibrillation

Circulation. 2010 Nov 30;122(22):2246-53. doi: 10.1161/CIRCULATIONAHA.110.973735.

Abstract

Background: The comparison of anticoagulants dabigatran and warfarin might be most equitable in vitamin K antagonist (VKA)-naive patients.

Methods and results: Warfarin and 2 doses of dabigatran-110 mg BID (D110) and 150 mg BID (D150)-were compared in a balanced population of VKA-naive (≤62 days of lifetime VKA exposure, with 33% never prescribed a VKA) and VKA-experienced patients with atrial fibrillation (n=18 113). For VKA-naive and -experienced patients assigned warfarin, the time in therapeutic range (international normalized ratio 2.0 to 3.0) was 62% and 67%, respectively, and 61% and 66% for those never and ever prescribed a VKA. In VKA-naive patients, stroke and systemic embolism rates were 1.57%, 1.07%, and 1.69% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.65); D150 was superior (P=0.005). Major bleeding rates were 3.11%, 3.34%, and 3.57% per year, respectively. D110 and D150 were similar to warfarin (P=0.19 and P=0.55). Intracranial bleeding rates were 0.19%, 0.33%, and 0.73% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 and P=0.005). In VKA-experienced patients, stroke and systemic embolism rates were 1.51%, 1.15%, and 1.74% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.32); D150 was superior (P=0.007). Major bleeding rates were 2.66%, 3.30%, and 3.57% per year, respectively. D110 was lower than warfarin (P=0.003); D150 was similar (P=0.41). Intracranial bleeding rates were 0.26%, 0.32%, and 0.79% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 for both). Results were similar for patients never on a VKA.

Conclusions: Previous VKA exposure does not influence the benefits of dabigatran at either dose compared with warfarin.

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

Publication types

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

MeSH terms

  • Aged
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / drug therapy*
  • Benzimidazoles / adverse effects
  • Benzimidazoles / therapeutic use*
  • Dabigatran
  • Dose-Response Relationship, Drug
  • Embolism / prevention & control
  • Female
  • Follow-Up Studies
  • Gastrointestinal Hemorrhage / epidemiology
  • Humans
  • Intracranial Hemorrhages / epidemiology
  • Male
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Risk Factors
  • Stroke / prevention & control
  • Treatment Outcome
  • Vitamin K / antagonists & inhibitors*
  • Warfarin / adverse effects
  • Warfarin / therapeutic use*

Substances

  • Anticoagulants
  • Benzimidazoles
  • Pyridines
  • Vitamin K
  • Warfarin
  • Dabigatran

Associated data

  • ClinicalTrials.gov/NCT00262600