Author + information
- Received January 10, 2013
- Revision received May 13, 2013
- Accepted May 21, 2013
- Published online September 3, 2013.
- John W. Eikelboom, MBBS∗∗ (, )
- Stuart J. Connolly, MD∗,
- Robert G. Hart, MD∗,
- Lars Wallentin, MD, PhD†,
- Paul Reilly, PhD‡,
- Jonas Oldgren, MD, PhD†,
- Sean Yang, MSc∗ and
- Salim Yusuf, MD, DPhil∗
- ∗Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
- †Uppsala Clinical Research Center and Department of Medical Sciences, Uppsala University, Uppsala, Sweden
- ‡Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut
- ↵∗Reprint requests and correspondence:
Dr. John W. Eikelboom, Population Health Research Institute, McMaster University, 237 Barton Street East, Hamilton, Ontario, Canada L8L 2X2.
Objectives This study sought to compare the net clinical benefit of dabigatran 110 mg bid and 150 mg bid with that of warfarin in patients with atrial fibrillation (AF).
Background In patients with AF, dabigatran 110 mg bid and 150 mg bid are associated with similar rates of death. However, the higher dose reduces ischemic stroke and increases bleeding compared with the lower dose. Therefore, there is uncertainty about how to evaluate the overall benefit of the 2 doses.
Methods In 18,113 AF patients in the RE-LY (Randomized Evaluation of Long Term Anticoagulant Therapy) trial, we used a previously developed method for integrating ischemic and bleeding events as “ischemic stroke equivalents” in order to compare a weighted benefit of 2 doses of dabigatran with each other, and with that of warfarin.
Results Compared with warfarin, there was a significant decrease in ischemic stroke equivalents with both dabigatran doses: –0.92 per 100 patient years (95% confidence interval [CI]: –1.74 to −0.21, p = 0.02) with dabigatran 110 mg bid and –1.08 (95% CI: –1.86 to −0.34, p = 0.01) with dabigatran 150 mg bid. There was no significant difference in ischemic stroke equivalents between the 2 doses: –0.16 (95% CI: –0.80 to 0.43) comparing dabigatran 150 mg bid with 110 bid. When including death in the weighted benefit calculations, the results were similar.
Conclusions On a group level both doses of dabigatran as compared with warfarin have similar benefits when considering a weighted estimate including both efficacy and safety. The similar overall benefits of the 2 doses of dabigatran versus warfarin support individualizing the dose based on patient characteristics and physician and patient preferences. (Randomized Evaluation of Long Term Anticoagulant Therapy [RE-LY] With Dabigatran Etexilate; NCT00262600)
The RE-LY trial was funded by Boehringer-Ingelheim. Dr. Eikelboom has received consulting fees/honoraria from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Pfizer, Janssen, and sanofi-aventis; and grants or in-kind support from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Pfizer, Janssen, and sanofi-aventis. Drs. Connolly, Hart, Wallentin, and Yusuf have received grant support/honoraria/consulting fees from Boehringer-Ingelheim. Dr. Oldgren has received grant support from Boehringer-Ingelheim; and consulting and lecture fees from Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, and Pfizer. Dr. Reilly is a full-time employee of Boehringer-Ingelheim. All other authors have reported that they haves no relationships relevant to the contents of this paper to disclose.
- Received January 10, 2013.
- Revision received May 13, 2013.
- Accepted May 21, 2013.
- American College of Cardiology Foundation