Author + information
- Received May 14, 2019
- Revision received July 9, 2019
- Accepted July 11, 2019
- Published online December 2, 2019.
- Michael Maeng, MD, PhDa,∗ (, )
- Philippe Gabriel Steg, MDb,c,d,e,
- Deepak L. Bhatt, MD, MPHf,
- Stefan H. Hohnloser, MDg,
- Matias Nordaby, MDh,
- Corinna Miede, MSci,
- Takeshi Kimura, MD, PhDj,
- Gregory Y.H. Lip, MDk,l,
- Jonas Oldgren, MD, PhDm,
- Jurriën M. ten Berg, MD, PhDn,
- Christopher P. Cannon, MDf,
- on behalf of the RE-DUAL PCI Steering Committee and Investigators
- aAarhus University Hospital, Aarhus, Denmark
- bFACT, an F-CRIN Network, DHU FIRE, Hôpital Bichat, Paris, France
- cUniversité Paris Diderot, Paris, France
- dINSERM U_1148, Paris, France
- eHôpital Bichat Assistance Publique–Hôpitaux de Paris, Paris, France
- fBrigham and Women’s Hospital and Heart and Vascular Center Harvard Medical School, Boston, Massachusetts
- gJohann Wolfgang Goethe University, Frankfurt am Main, Germany
- hBoehringer Ingelheim International, Ingelheim, Germany
- iHMS Analytical Software, Weimar (Lahn), Germany
- jKyoto University, Kyoto, Japan
- kLiverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom
- lAalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- mUppsala Clinical Research Center and Department of Medical Sciences, Uppsala University, Uppsala, Sweden
- nSt. Antonius Ziekenhuis, Nieuwegein, the Netherlands
- ↵∗Address for correspondence:
Dr. Michael Maeng, Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark.
Objectives The aim of this study was to evaluate dabigatran dual therapy versus warfarin triple therapy in patients with or without diabetes mellitus in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial.
Background It is unclear whether dual therapy is as safe and efficacious as triple therapy in patients with atrial fibrillation with diabetes following percutaneous coronary intervention.
Methods In RE-DUAL PCI, 2,725 patients with atrial fibrillation (993 with diabetes) who had undergone PCI were assigned to warfarin triple therapy (warfarin, clopidogrel or ticagrelor, and aspirin) or dabigatran dual therapy (dabigatran 110 mg or 150 mg twice daily and clopidogrel or ticagrelor). Median follow-up was 13 months. The primary outcome was the composite of major bleeding or clinically relevant nonmajor bleeding, and the main efficacy outcome was the composite of death, thromboembolic events, or unplanned revascularization.
Results Among patients with diabetes, the incidence of major bleeding or clinically relevant nonmajor bleeding was 15.2% in the dabigatran 110 mg dual therapy group versus 27.5% in the warfarin triple therapy group (hazard ratio [HR]: 0.48; 95% confidence interval [CI] 0.35 to 0.67) and 23.8% in the dabigatran 150 mg dual therapy group versus 25.1% in the warfarin triple therapy group (HR: 0.87; 95% CI: 0.62 to 1.22). Risk for major bleeding or clinically relevant nonmajor bleeding was also reduced with both dabigatran doses among patients without diabetes (dabigatran 110 mg dual therapy: HR: 0.54; 95% CI: 0.42 to 0.70; dabigatran 150 mg dual therapy: HR: 0.63; 95% CI: 0.48 to 0.83). Risk for the efficacy endpoint was comparable between treatment groups for both patients with and those without diabetes. No interaction between treatment and diabetes subgroup could be observed, either for bleeding or for composite efficacy endpoints.
Conclusions In this subgroup analysis, dabigatran dual therapy had a lower risk for bleeding and a comparable rate of the efficacy endpoint compared with warfarin triple therapy in patients with atrial fibrillation with or without diabetes following percutaneous coronary intervention.
This work was supported by Boehringer Ingelheim International. Dr. Maeng has received personal fees from Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Novo Nordisk, and AstraZeneca. Dr. Steg has received research grants from Bayer HealthCare, Merck, Sanofi, and Servier; and has received speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer/Janssen, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, Merck, Novartis, Novo Nordisk, Pfizer, Regeneron, Sanofi, and Servier. Dr. Bhatt is an advisory board member for Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, and Regado Biosciences; is a member of the boards of directors of the Boston VA Research Institute, the Society of Cardiovascular Patient Care, and TobeSoft; is chair of the American Heart Association Quality Oversight Committee; is a member of data monitoring committees for the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), the Cleveland Clinic (including for the ExCEED trial, funded by Edwards Lifesciences), the Duke Clinical Research Institute, the Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo), and the Population Health Research Institute; has received honoraria from the American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; vice chair, ACC Accreditation Committee), the Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim), Belvoir Publications (editor-in-chief, Harvard Heart Letter), the Duke Clinical Research Institute (clinical trial steering committees), HMP Global (editor-in-chief, Journal of Invasive Cardiology), the Journal of the American College of Cardiology (guest editor, associate editor), Medtelligence/ReachMD (continuing medical education steering committees), the Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and U.S. national coleader, funded by Bayer), Slack Publications (chief medical editor, Cardiology Today’s Intervention), the Society of Cardiovascular Patient Care (secretary/treasurer), WebMD (continuing medical education steering committees); is deputy editor of Clinical Cardiology; is chair of the NCDR-ACTION Registry Steering Committee and the VA CART Research and Publications Committee; has received research funding from Abbott, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, Regeneron, Roche, Sanofi, Synaptic, and The Medicines Company; has received royalties from Elsevier (editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); is a site co-investigator for Biotronik, Boston Scientific, St. Jude Medical (now Abbott), and Svelte; is a trustee of the American College of Cardiology; and has conducted unfunded research for FlowCo, Fractyl, Merck, Novo Nordisk, PLx Pharma, and Takeda. Dr. Hohnloser has received personal fees from Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Medtronic, Pfizer, St. Jude Medical, and Zol. Dr. Nordaby is an employee of Boehringer Ingelheim International. Ms. Miede is an employee of HMS Analytical Software, contracted by Boehringer Ingelheim International. Dr. Kimura has received grants from Boehringer Ingelheim. Dr. Lip has served as a consultant for Bayer/Janssen, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon, and Daiichi-Sankyo; and has been a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, and Medtronic (no fees are personally received). Dr. Oldgren has received fees to his institution from Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Pfizer, and Sanofi. Dr. ten Berg has received advisory, consulting, and speaking fees from Accumetrics, AstraZeneca, Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Ferrer, The Medicines Company, and Pfizer; and has received research grants from AstraZeneca and ZonMw. Dr. Cannon has received research grants from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Janssen, and Merck; and has received consulting fees from Alnylam, Amarin, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Janssen, Kowa, Merck, Pfizer, Regeneron, and Sanofi.
- Received May 14, 2019.
- Revision received July 9, 2019.
- Accepted July 11, 2019.
- 2019 The Authors