Author + information
- Received April 15, 2019
- Revision received August 23, 2019
- Accepted August 27, 2019
- Published online December 2, 2019.
- Jurrien M. ten Berg, MD, PhDa,∗∗ (, )
- Anne de Veer, MDa,∗,
- Jonas Oldgren, MD, PhDb,
- Philippe Gabriel Steg, MDc,d,e,f,
- Dmitry A. Zateyshchikov, MD, PhD, DrSci(Med)g,
- Petr Jansky, MDh,
- Ki-Bae Seung, MDi,
- Stefan H. Hohnloser, MDj,
- Gregory Y.H. Lip, MDk,l,
- Matias Nordaby, MDm,
- Eva Kleine, MScm,
- Deepak L. Bhatt, MD, MPHn,
- Christopher P. Cannon, MDn,
- on behalf of the RE-DUAL PCI Steering Committee and Investigators
- aSt. Antonius Ziekenhuis, Nieuwegein, the Netherlands
- bUppsala Clinical Research Center and Department of Medical Sciences, Uppsala University, Uppsala, Sweden
- cFrench Alliance for Cardiovascular Trials, Département Hospitalo-Universitaire FIRE, Paris, France
- dUniversité de Paris, Paris, France
- eINSERM U-1148, Paris, France
- fHôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France
- gPrimary Vascular Department, City Clinic Hospital #51, Moscow, Russian Federation
- hDepartment of Cardiovascular Surgery, Faculty Hospital Motol, Prague, Czech Republic
- iThe Catholic University of Korea, Seoul, Korea
- jJohann Wolfgang Goethe University, Frankfurt am Main, Germany
- 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
- mBoehringer Ingelheim International, Ingelheim, Germany
- nBrigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Jurrien M. ten Berg, St. Antonius Ziekenhuis, Department of Cardiology, Koekoekslaan 1, 3430 EM, Nieuwegein, the Netherlands.
Objectives The aim of this study was to assess if prior oral anticoagulant agent (OAC) use modifies the lower bleeding risk observed with dabigatran dual therapy (dabigatran twice daily plus a P2Y12 inhibitor) versus warfarin triple therapy (warfarin plus a P2Y12 inhibitor plus aspirin) in patients with atrial fibrillation who underwent percutaneous coronary intervention (PCI).
Background 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, the primary outcome of major bleeding or clinically relevant nonmajor bleeding was lower with dabigatran dual therapy versus warfarin triple therapy in patients with atrial fibrillation who underwent PCI.
Methods A total of 2,725 patients were randomized to dual therapy with dabigatran (110 or 150 mg twice daily) plus clopidogrel or ticagrelor or triple therapy with warfarin plus aspirin and clopidogrel or ticagrelor. Subgroup analysis compared risk for major bleeding or clinically relevant nonmajor bleeding and a composite thromboembolic endpoint in patients with prior OAC use and in those who were OAC treatment naive.
Results Risk for major bleeding or clinically relevant nonmajor bleeding was reduced with both dabigatran dual therapies compared with warfarin triple therapy in both the prior OAC use group (hazard ratios: 0.58 [95% confidence interval (CI): 0.42 to 0.81] and 0.61 [95% CI: 0.41 to 0.92] with 110 and 150 mg dabigatran, respectively) and the OAC-naive group (hazard ratios: 0.49 [95% CI: 0.38 to 0.63] and 0.76 [95% CI: 0.59 to 0.97] with 110 and 150 mg dabigatran) (p for interaction = 0.42 and 0.37, 110 and 150 mg dabigatran, respectively). The risk for thromboembolic events seemed similar with dabigatran dual therapy (both doses) and warfarin triple therapy across subgroups.
Conclusions Bleeding risk was reduced with dabigatran dual therapy versus warfarin triple therapy in patients with atrial fibrillation after PCI, regardless of whether they were prior OAC users or OAC treatment naive. These results suggest that it is also safe to switch patients on OAC pre-PCI to dabigatran dual therapy post-PCI.
↵∗ Drs. ten Berg and de Veer contributed equally to this paper.
This work was supported by Boehringer Ingelheim International. Dr. ten Berg has received advisory, consulting, and speaking 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. de Veer has received consulting fees from Bayer and Boehringer Ingelheim. Dr. Oldgren has received fees to his institution from AstraZeneca, Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Pfizer, Portola, Roche Diagnostics, and Sanofi. Dr. Steg has received research grants from Amarin, Bayer, Sanofi, and Servier; and has received speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer/Janssen, Boehringer Ingelheim, Bristol-Myers Squibb, Idorsia, Lilly, Merck, Novartis, Novo Nordisk, Pfizer, Regeneron, Sanofi, and Servier. Dr. Zateyshchikov has received lecture and advisory board honoraria from Boehringer Ingelheim, AstraZeneca, KRKA, Takeda, Sanofi, Bayer, Aspen, and Pfizer. Dr. Jansky has received advisory and speaking fees from Boehringer Ingelheim, Bayer, Pfizer, Sanofi, and Amgen. Dr. Hohnloser has received personal fees from Abbott (St. Jude Medical), Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Johnson & Johnson, Medtronic, Pfizer, and Sanofi; and has received lecture fees from Abbott (St. Jude Medical), Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, and Pfizer. Dr. Lip has received consulting fees from Bayer/Janssen, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon, and Daiichi-Sankyo; and has received speaking fees from Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo (no fees are directly received personally). Dr. Nordaby and Ms. Kleine are employees of Boehringer Ingelheim International. Dr. Bhatt is an advisory board member for Cardax, Cereno Scientific, 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; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor-in-chief, Harvard Heart Letter), the Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), 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, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, 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. Cannon has received research grants from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Janssen, Merck, and Pfizer; and has received consulting fees from Aegerion, Alnylam, Amarin, Amgen, Applied Therapeutics, Ascendia, BGB, Boehringer Ingelheim, Bristol-Myers Squibb, Corvidia, HLS Therapeutics, Innovent, Janssen, Kowa, Merck, Pfizer, and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received April 15, 2019.
- Revision received August 23, 2019.
- Accepted August 27, 2019.
- 2019 American College of Cardiology Foundation
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.