Evaluation of dabigatran bleeding adverse reaction reports in the FDA adverse event reporting system during the first year of approval

Pharmacotherapy. 2014 Jun;34(6):561-9. doi: 10.1002/phar.1415. Epub 2014 Mar 19.


Study objective: Evaluate dabigatran adverse event reports with a reported bleeding event and/or reported fatal outcome compared with warfarin.

Design: Retrospective analysis of the FDA Adverse Event Reporting System (FAERS) database.

Measurements and main results: We identified reports from October 1, 2010, through December 31, 2011, in the United States listing dabigatran or warfarin as the primary suspected agent. Bleeding events and related outcomes were determined. A bleeding-related mortality rate was calculated based on national dabigatran treatment data.

Results: Dabigatran was the primary suspected agent in 9029 adverse reports. Of these, 2347 (26%) were bleeding events; a fatal outcome was reported in 348 (15%) of the bleeding events. In comparison, warfarin was the suspected agent in 2038 reports, of which 647 (32%) were reported as bleeding events. Among the warfarin bleeding reports, 46 (7.1%) reported a fatal outcome. Based on national dabigatran use and adverse bleed reports with fatal outcomes, we estimate a lower bound of 150 bleeding-related fatalities per 100,000 dabigatran patient-years. Because of underreporting bias, these estimates represent a lower bound on the population bleeding mortality rates.

Conclusion: Reports from FAERS are subject to significant bias but suggest that fatal outcomes among dabigatran reports are higher in clinical practice than they were in controlled clinical trials.

Keywords: atrial fibrillation; bleeding; dabigatran; stroke prevention; warfarin.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adverse Drug Reaction Reporting Systems
  • Aged
  • Aged, 80 and over
  • Anticoagulants / adverse effects
  • Antithrombins / adverse effects*
  • Benzimidazoles / adverse effects*
  • Dabigatran
  • Databases, Factual
  • Female
  • Hemorrhage / chemically induced*
  • Hemorrhage / epidemiology
  • Hemorrhage / mortality
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • United States / epidemiology
  • United States Food and Drug Administration
  • Warfarin / adverse effects*
  • beta-Alanine / adverse effects
  • beta-Alanine / analogs & derivatives*


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