title: Design and Rationale of the RE-DUAL PCI Trial: A Prospective, Randomized, Phase 3b Study Comparing the Safety and Efficacy of Dual Antithrombotic Therapy With Dabigatran Etexilate Versus Warfarin Triple Therapy in Patients With Nonvalvular Atrial Fibrillation Who Have Undergone Percutaneous Coronary Intervention With Stenting.
abstract: Antithrombotic management of patients with atrial fibrillation (AF) undergoing coronary stenting is complicated by the need for anticoagulant therapy for stroke prevention and dual antiplatelet therapy for prevention of stent thrombosis and coronary events. Triple antithrombotic therapy, typically comprising warfarin, aspirin, and clopidogrel, is associated with a high risk of bleeding. A modest-sized trial of oral anticoagulation with warfarin and clopidogrel without aspirin showed improvements in both bleeding and thrombotic events compared with triple therapy, but large trials are lacking. The RE-DUAL PCI trial (NCT 02164864) is a phase 3b, a strategy of prospective, randomized, open-label, blinded-endpoint trial. The main objective is to evaluate dual antithrombotic therapy with dabigatran etexilate (110 or 150 mg twice daily) and a P2Y12 inhibtor (either clopidogrel or ticagrelor) compared with triple antithrombotic therapy with warfarin, a P2Y12 inhibtor (either clopidogrel or ticagrelor, and low-dose aspirin (for 1 or 3 months, depending on stent type) in nonvalvular AF patients who have undergone percutaneous coronary intervention with stenting. The primary endpoint is time to first International Society of Thrombosis and Hemostasis major bleeding event or clinically relevant nonmajor bleeding event. Secondary endpoints are the composite of all cause death or thrombotic events (myocardial infarction, or stroke/systemic embolism) and unplanned revascularization; death or thrombotic events; individual outcome events; death, myocardial infarction, or stroke; and unplanned revascularization. A hierarchical procedure for multiple testing will be used. The plan is to randomize ∼ 2500 patients at approximately 550 centers worldwide to try to identify new treatment strategies for this patient population.
authors: Harvard Clinical Research Institute, Boston, Massachusetts. christopher.cannon@hcri.harvard.edu.|Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts. christopher.cannon@hcri.harvard.edu.|Harvard Medical School, Boston, Massachusetts. christopher.cannon@hcri.harvard.edu.
authors: Christopher P
authors: CP
authors: Cannon
authors: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany.
authors: Savion
authors: S
authors: Gropper
authors: Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.|Harvard Medical School, Boston, Massachusetts.
authors: Deepak L
authors: http://orcid.org/0000-0002-1278-6245
authors: DL
authors: Bhatt
authors: Cleveland Clinic, Cleveland, Ohio.
authors: Stephen G
authors: SG
authors: Ellis
authors: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Takeshi
authors: T
authors: Kimura
authors: University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom.
authors: Gregory Y H
authors: GY
authors: Lip
authors: FACT (French Alliance for Cardiovascular Trials), an F-CRIN network, Département Hospitalo-Universitaire FIRE, AP-HP, Hôpital Bichat, Université Paris-Diderot, Sorbonne Paris-Cité, INSERM U-1148, Paris, France.|NHLI Imperial College, ICMS Royal Brompton Hospital, London, United Kingdom.
authors: Ph Gabriel
authors: PG
authors: Steg
authors: St. Antonius Hospital, Nieuwegein, The Netherlands.
authors: Jurriën M
authors: JM
authors: Ten Berg
authors: Medical Division Boehringer Ingelheim Ltd, Bracknell, Berkshire, United Kingdom.
authors: Jenny
authors: J
authors: Manassie
authors: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany.|Faculty of Medicine, University of Heidelberg, Heidelberg, Germany.
authors: Jörg
authors: J
authors: Kreuzer
authors: Medical Division Boehringer Ingelheim Ltd, Bracknell, Berkshire, United Kingdom.
authors: Jon
authors: http://orcid.org/0000-0001-9354-9657
authors: J
authors: Blatchford
authors: Boston University School of Public Health, Boston, Massachusetts.
authors: Joseph M
authors: JM
authors: Massaro
authors: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany.|Faculty of Medicine Mannheim of the University of Heidelberg, Mannheim, Germany.
authors: Martina
authors: M
authors: Brueckmann
authors: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany.
authors: Ernesto
authors: E
authors: Ferreiros Ripoll
authors: Department of Medical Sciences and Uppsala Clinical Research Centre, Uppsala University Hospital, Uppsala, Sweden.
authors: Jonas
authors: J
authors: Oldgren
authors: Department of Cardiology, J.W. Goethe University, Frankfurt, Germany.
authors: Stefan H
authors: SH
authors: Hohnloser
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D000991:Antithrombins / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D002985:Clinical Protocols; D003324:Coronary Artery Disease / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D003328:Coronary Thrombosis / Q000209:etiology / Q000517:prevention & control; D000069604:Dabigatran / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000295:instrumentation* / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D012107:Research Design; D012307:Risk Factors; D015607:Stents; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D013997:Time Factors; D016896:Treatment Outcome; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D014859:Warfarin; D000069604:Dabigatran
keywords: Anti platelet therapy; Arrhythmia/all; Cardiac; Clinical trials; General clinical cardiology; Pharmacology; Stroke prevention; Thrombosis/hypercoagulable states; catheterization/diagnostic interventional; management