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

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.