Author + information
- Received December 23, 2014
- Revision received March 27, 2015
- Accepted March 31, 2015
- Published online June 16, 2015.
- Michael Böhm, MD∗∗ (, )
- Michael D. Ezekowitz, MD, ChB, DPhil†,‡,
- Stuart J. Connolly, MD§,
- John W. Eikelboom, MBBS§,
- Stefan H. Hohnloser, MD‖,
- Paul A. Reilly, PhD¶,
- Helmut Schumacher, PhD#,
- Martina Brueckmann, MD#∗∗,
- Stephan H. Schirmer, MD, PhD∗,
- Mario T. Kratz, MD∗,
- Salim Yusuf, MD, DPhil§,
- Hans-Christoph Diener, MD††,
- Ziad Hijazi, MD‡‡ and
- Lars Wallentin, MD, PhD‡‡
- ∗Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg, Germany
- †Sidney Kimmel Medical College at Jefferson University, Philadelphia, Pennsylvania
- ‡Lankenau Institute for Medical Research and The Heart Center, Wynnewood, Pennsylvania
- §Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada
- ‖Department of Cardiology, J.W. Goethe University, Frankfurt/Main, Germany
- ¶Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut
- #Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany
- ∗∗Faculty of Medicine Mannheim at the University of Heidelberg, Heidelberg, Germany
- ††Department of Neurology, Universitätsklinikum Duisburg-Essen, Essen, Germany
- ‡‡Uppsala Clinical Research Center and Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
- ↵∗Reprint requests and correspondence:
Prof. Dr. med. Michael Böhm, Universitätsklinikum des Saarlandes, Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Kirrberger Strasse 100, 66421 Homburg/Saar, Germany.
Background Vitamin K–dependent factors protect against vascular and renovascular calcification, and vitamin K antagonists may be associated with a decreased glomerular filtration rate (GFR).
Objectives This study analyzed changes in GFR during long-term treatment with warfarin or dabigatran etexilate (DE) in patients enrolled in the RE-LY (Randomized Evaluation of Long Term Anticoagulation Therapy) trial.
Methods Of the 18,113 patients in the RE-LY study randomized to receive DE (110 mg or 150 mg twice daily) or warfarin, 16,490 patients with atrial fibrillation had creatinine values measured at baseline and at least 1 follow-up visit. Changes in GFR for up to 30 months were evaluated.
Results GFR declined in all treatment groups. After an average of 30 months, the mean ± SE decline in GFR was significantly greater with warfarin (–3.68 ± 0.24 ml/min) compared with DE 110 mg (–2.57 ± 0.24 ml/min; p = 0.0009 vs. warfarin) and DE 150 mg (–2.46 ± 0.23 ml/min; p = 0.0002 vs. warfarin). A decrease in GFR >25% was less likely with DE 110 mg (hazard ratio: 0.81 [95% confidence interval: 0.69 to 0.96]; p = 0.017) or DE 150 mg (hazard ratio: 0.79 [95% confidence interval: 0.68 to 0.93]; p = 0.0056) than with warfarin in the observation period >18 months. Patients with poor international normalized ratio control (i.e., time in therapeutic range <65%) exhibited a faster decline in GFR. A more pronounced decline in GFR was associated with previous warfarin use and with the presence of diabetes.
Conclusions Patients with atrial fibrillation receiving oral anticoagulation exhibited a decline in renal function that was greater in those taking warfarin versus DE, and it was amplified by diabetes and previous vitamin K antagonist use. (Randomized Evaluation of Long Term Anticoagulant Therapy [RE-LY] With Dabigatran Etexilate; NCT00262600)
The RE-LY (Randomized Evaluation of Long Term Anticoagulation Therapy) trial was funded by Boehringer Ingelheim, Germany. All authors received scientific support from Boehringer Ingelheim. Dr. Böhm is supported by the Deutsche Forschungsgesellschaft (KFO 196) and has received consulting/honoraria fees from Boehringer Ingelheim, Bayer, Servier, and Medtronic. Dr. Ezekowitz is a consultant for and/or has received consulting/honoraria fees from Boehringer Ingelheim, Pfizer, Sanofi, Bristol-Myers Squibb, Portola, Bayer, Daiichi-Sankyo, Medtronic, Aegerion, Merck, Johnson & Johnson, Gilead, Janssen Scientific Affairs, Pozen Inc., Amgen, Coherex, and Armetheon. Dr. Connolly has received consulting and research grants from Boehringer Ingelheim. Dr. Eikelboom has received consulting/honoraria fees from Bayer, Boehringer Ingelheim, AstraZeneca, Bristol-Myers Squibb/Pfizer, Sanofi, Daiichi-Sankyo, and Eli Lilly. Dr. Hohnloser has received consulting/honoraria fees from Boehringer Ingelheim, Bayer, Bristol-Myers Squibb, Pfizer, Daiichi-Sankyo, Sanofi, St. Jude Medical, Portola, Gilead, Medtronic, and Zoll. Dr. Schirmer has received a travel allowance/research funding/speakers honoraria from Boehringer Ingelheim. Dr. Yusuf has received research grants from Boehringer Ingelheim. Dr. Diener received honoraria for participation in clinical trials, contribution to advisory boards and oral presentations from Boehringer Ingelheim. Dr. Hijazi has received institutional research grants from Boehringer Ingelheim and Bristol-Myers Squibb/Pfizer. Dr. Wallentin has received research grants, consultancy and lecture fees, honoraria, and travel support from AstraZeneca, Bristol-Myers Squibb/Pfizer, and GlaxoSmithKline; research grants, consultancy and lecture fees, and honoraria from Boehringer Ingelheim; research grants and consultancy fees from Merck & Co.; and consultancy fees from Abbott, Athera Biotechnologies, and Regado Biosciences. Drs. Schumacher and Brueckmann are employees of Boehringer Ingelheim, Germany. Dr. Reilly is an employee of Boehringer Ingelheim, Pharmaceuticals, USA. Dr. Kratz has reported that he has no relationships relevant to the contents of this paper to disclose.
- Received December 23, 2014.
- Revision received March 27, 2015.
- Accepted March 31, 2015.
- American College of Cardiology Foundation