title: Net clinical benefit of dabigatran vs. warfarin in venous thromboembolism: analyses from RE-COVER®, RE-COVER™ II, and RE-MEDY™.
abstract: The direct oral anticoagulants, e.g., dabigatran etexilate (DE), are effective and well tolerated treatments for venous thromboembolism (VTE). Net clinical benefit (NCB) is a useful concept in weighing potential benefits against potential harm of comparator drugs. The NCB of DE vs. warfarin in VTE treatment was compared. Post-hoc analyses were performed on pooled data from the 6-month RE-COVER® and RE-COVER™ II trials, and data from the RE-MEDY™ trial (up to 36 months), to compare the NCB of DE (150 mg twice daily) and warfarin [target international normalized ratio (INR) 2.0-3.0]. Patients (≥18 years old) had symptomatic proximal deep vein thrombosis and/or pulmonary embolism. NCB was the composite of cardiovascular endpoints (non-fatal events of recurrent VTE, myocardial infarction, stroke or systemic embolism), all-cause death, and bleeding outcomes, all weighted equally. A broad definition of NCB included major bleeding events (MBE) and clinically relevant non-major bleeding events as bleeding outcomes, while a narrow definition included just MBE. The pooled dataset totalled 5107 patients from RE-COVER/RE-COVER II and 2856 patients from RE-MEDY. When NCB was narrowly defined, NCB was similar between DE and warfarin. When broadly defined, NCB was superior with DE vs. warfarin [RE-COVER/RE-COVER II, hazard ratio (HR) 0.80; 95% confidence interval (CI), 0.68-0.95 and RE-MEDY, HR 0.73; 95% CI 0.59-0.91]. These findings were unaffected by warfarin time in therapeutic range. The NCB of DE was similar or superior to warfarin, depending on the NCB definition used, regardless of the quality of INR control.
authors.affiliation: Boehringer Ingelheim GmbH & Co. KG, 55216, Ingelheim am Rhein, Germany. martin.feuring@boehringer-ingelheim.com.
authors.forename: Martin
authors.initials: M
authors.lastname: Feuring
authors.affiliation: Department of Medicine, McMaster University and Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada.
authors.forename: Sam
authors.initials: S
authors.lastname: Schulman
authors.affiliation: Department of Medicine, Sahlgrenska University Hospital-Östra, Gothenburg, Sweden.
authors.forename: Henry
authors.initials: H
authors.lastname: Eriksson
authors.affiliation: Thrombosis Research Institute and University College London, London, UK.
authors.forename: Ajay J
authors.initials: AJ
authors.lastname: Kakkar
authors.affiliation: Medical Division 2, Municipal Hospital Dresden-Friedrichstadt, Dresden, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schellong
authors.affiliation: Boehringer Ingelheim GmbH & Co. KG, 55216, Ingelheim am Rhein, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hantel
authors.affiliation: Accovion GmbH, Eschborn, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Schueler
authors.affiliation: Boehringer Ingelheim GmbH & Co. KG, 55216, Ingelheim am Rhein, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuzer
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Samuel Z
authors.initials: SZ
authors.lastname: Goldhaber
mesh_terms: D000328:Adult; D000368:Aged; D002986:Clinical Trials as Topic; D000069604:Dabigatran / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction; D011655:Pulmonary Embolism; D020521:Stroke; D054556:Venous Thromboembolism / Q000150:complications / Q000188:drug therapy*; D020246:Venous Thrombosis; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D014859:Warfarin; D000069604:Dabigatran
keywords: Anticoagulant; Dabigatran etexilate; Venous thromboembolism; Warfarin