Author + information
- Received January 28, 2019
- Revision received April 17, 2019
- Accepted May 21, 2019
- Published online August 19, 2019.
- Stefan H. Hohnloser, MDa,∗ (, )
- Philippe Gabriel Steg, MDb,c,d,e,
- Jonas Oldgren, MD, PhDf,
- Georg Nickenig, MDg,
- Robert G. Kiss, MD, PhDh,
- Zeki Ongen, MDi,
- Jose L. Navarro Estrada, MDj,
- Ton Oude Ophuis, MD, PhDk,
- Gregory Y.H. Lip, MDl,m,
- Matias Nordaby, MDn,
- Eva Kleine, MScn,
- Jurrien M. ten Berg, MDo,
- Deepak L. Bhatt, MD, MPHp,
- Christopher P. Cannon, MDp,
- on behalf of the RE-DUAL PCI Steering Committee and Investigators
- aDepartment of Cardiology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany
- bDépartement Hospitalo-Universitaire, French Alliance for Cardiovascular Trials (FACT), Hôpital Bichat, Paris, France
- cUniversité Paris Diderot, Paris, France
- dINSERM U_1148, Paris, France
- eHôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France
- fUppsala Clinical Research Center and Department of Medical Sciences, Uppsala, Sweden
- gMedizinische Klinik und Poliklinik II, University of Bonn, Bonn, Germany
- hMedical Centre, Hungarian Defence Forces, Budapest, Hungary
- iDepartment of Cardiology, Istanbul University Cerrahpasa, Istanbul, Turkey
- jDepartment of Cardiology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
- kDepartment of Cardiology, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands
- lLiverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom
- mAalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- nBoehringer Ingelheim International GmbH, Ingelheim, Germany
- oDepartment of Cardiology, St. Antonius Ziekenhuis, Nieuwegein, the Netherlands
- pBrigham and Women’s Hospital Heart and Vascular Center, and Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Stefan H. Hohnloser, Department of Cardiology, Johann Wolfgang Goethe University, Theodor Stern Kai 7, Building 23A, 60590 Frankfurt am Main, Germany.
Objectives The study sought to evaluate the effect of dabigatran dual therapy versus warfarin triple therapy across categories of renal function 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 The RE-DUAL PCI (NCT02164864) trial of patients with atrial fibrillation undergoing percutaneous coronary intervention reported that dabigatran dual therapy (110 or 150 mg twice daily, plus clopidogrel or ticagrelor) reduced the primary endpoint of major bleeding events (MBE) or clinically relevant nonmajor bleeding events (CRNMBE) compared with warfarin triple therapy, with noninferiority in overall thromboembolic events.
Methods Risk of a first MBE or CRNMBE and the composite of death or thromboembolic event (DTE) or unplanned revascularization were evaluated in 2,725 patients according to baseline creatinine clearance (CrCl) categories: 30 to <50, 50 to <80, and ≥80 ml/min.
Results Compared with warfarin, dabigatran 110 mg dual therapy reduced risk of MBE or CRNMBE across all categories of CrCl (p for interaction = 0.19). Dabigatran 150 mg dual therapy reduced risk of MBE or CRNMBE regardless of the CrCl category (p for interaction = 0.31). Risk of DTE or unplanned revascularization was similar to warfarin triple therapy for dabigatran 110 mg dual therapy across all CrCl categories. Dabigatran 150 mg dual therapy versus warfarin triple therapy had similar risk for DTE or unplanned revascularization in patients with CrCl 30 to <80 ml/min and lower risk at CrCl ≥80 ml/min (p for interaction = 0.02).
Conclusions In the RE-DUAL PCI trial, dabigatran dual therapy reduced bleeding events versus warfarin triple therapy irrespective of renal function, with overall similar risks of thromboembolic events but lower risks with dabigatran 150 mg in patients with normal CrCl.
- atrial fibrillation
- dabigatran dual therapy
- percutaneous coronary intervention
- renal function
- warfarin triple therapy
This work was supported by Boehringer Ingelheim International GmbH, Ingelheim, Germany. Dr. Hohnloser has received personal fees from Bayer Healthcare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Medtronic, Pfizer, St. Jude Medical, and Zoll. Dr. Steg has received research grants from Bayer HealthCare, Merck, Sanofi, and Servier; 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. Oldgren has received fees to his institution from AstraZeneca, Boehringer Ingelheim, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Pfizer, Portola, Roche Diagnostics, and Sanofi. Dr. Nickenig has received personal fees and grants from Abbott, Bayer Healthcare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Edwards, Medtronic, Mitratech, Novartis, Pfizer, Sanofi, and Zoll. Dr. Kiss has received honoraria as a speaker from Bayer, Boehringer Ingelheim, Merck Sharp and Dohme, and Pfizer. Dr. Ongen has received advisory-speaker fees from Bayer, Boehringer Ingelheim, and Daiichi-Sankyo. Dr. Navarro Estrada has received advisory-speaker fees from AstraZeneca, Boehringer Ingelheim, and Sanofi. Dr. Oude Ophuis has received advisory, consulting, and speaker fees from Amgen, AstraZeneca, Bristol-Myers Squibb, and Medtronic. 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, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. Dr. Nordaby and Ms. Kleine are employees of Boehringer Ingelheim International GmbH. Dr. ten Berg has received advisory, consulting, and speaker fees from Accumetrics, AstraZeneca, Bayer, 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. Bhatt has served on the Advisory Board for Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, and Regado Biosciences; has served on the Board of Directors for Boston VA Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; has served as the Chair of the American Heart Association Quality Oversight Committee, NCDR-ACTION Registry Steering Committee, and VA CART Research and Publications Committee; has served on the 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), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), and 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), 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), Duke Clinical Research Institute (clinical trial steering committees), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Medtelligence/ReachMD (CME steering committees), Population Health Research Institute (COMPASS clinical trial steering committee funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME Steering Committees); has served as the Deputy Editor for Clinical Cardiology; 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 Aventis, Synaptic, and The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has served as a site co-investigator for Biotronik, Boston Scientific, St. Jude Medical (now Abbott), and Svelte; has served as a trustee for the American College of Cardiology; and has conducted unfunded research for FlowCo, Fractyl, Merck, Novo Nordisk, PLx Pharma, and Takeda. Dr. Cannon has received research grants from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Janssen, and Merck; and consulting fees from Alnylam, Amarin, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, Janssen, Kowa, Merck, Pfizer, Regeneron, and Sanofi.
- Received January 28, 2019.
- Revision received April 17, 2019.
- Accepted May 21, 2019.
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