Original articleAlimentary tractAnalysis of Upper Gastrointestinal Adverse Events Among Patients Given Dabigatran in the RE-LY Trial
Section snippets
RE-LY Trial Design
All analyses were performed using the database from the RE-LY trial (N = 18,113).1, 8 Briefly, the RE-LY trial compared double-blind doses of dabigatran etexilate 110 mg twice daily and 150 mg twice daily with open-label warfarin (target international normalized ratio, 2.0–3.0) in patients with atrial fibrillation. The median follow-up period was 2 years, the primary efficacy outcome was prevention of stroke or systemic embolism, and the main safety outcome was major bleeding. Because the
Rate of Upper Gastrointestinal Adverse Events
The mean duration of treatment with dabigatran was 21.7 months, and the mean duration of treatment with warfarin was 22.6 months. Overall, the NB-UGI AEs at the 2 dabigatran doses (110 mg twice daily and 150 mg twice daily) during the course of the trial were not significantly different (17.6% and 16.3%, respectively; RR, 0.93; 95% CI, 0.86–1.00; P = .06) Likewise, there was no dose response within the individual NB-UGI AE subgroups (gastroesophageal reflux, P = .08; upper abdominal
Discussion
Dabigatran, a new oral, direct thrombin inhibitor, recently was approved for the prevention of stroke and deep venous thromboembolic events, and represents an alternative to warfarin. In the pivotal phase 3 trials, the overall safety profile for dabigatran vs warfarin was favorable, except for a relative increase in dyspepsia-like symptoms and (at the higher dabigatran dose) GI bleeding events. The pathophysiology of these adverse GI effects is not known, and the optimal strategy to prevent or
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Conflicts of interest These authors disclose the following: Peter Bytzer is a member of the Advisory Boards of Boehringer Ingelheim, AstraZeneca, Wyeth, Eisai, Janssen-Cilag, Nycomed, and Reckitt Benckiser; has received grants from AstraZeneca and Reckitt Benckiser; and is a member of the Speakers Bureau for AstraZeneca and Eisai. James Aisenberg is a consultant for Boehringer Ingelheim and has received research support from Merck. Stuart Connolly, co-principal investigator for RE-LY, is a consultant for Boehringer Ingelheim and has received research grants and lecture fees from Boehringer Ingelheim. Michael Ezekowitz, Co–PI for RE-LY, is a consultant for Boehringer Ingelheim, ARYx Therapeutics, Pfizer, Sanofi, Bristol Myers Squibb, Portola, AstraZeneca, Diachi Sanko, Eisai, and Medtronic. Stephan Formella is a full-time employee of Boehringer Ingelheim. Paul Reilly is a Clinical Project Leader for RE-LY and a full-time employee of Boehringer Ingelheim. The remaining author discloses no conflicts.
Funding Supported by Boehringer Ingelheim Pharmaceuticals.