title: Effectiveness and outcome of management strategies for dabigatran- or warfarin-related major bleeding events.
abstract: BACKGROUND
  Strategies used for the management of dabigatran-related major bleeding events (MBEs), and their effectiveness have not been systematically evaluated.
  
  
  METHODS
  Reports on 1034 individuals experiencing 1121 MBEs (696 on dabigatran, and 425 on warfarin) in 5 phase III randomized controlled trials were assessed independently by two investigators.
  
  
  RESULTS
  MBEs were managed either by drug discontinuation only (37%), or drug discontinuation with either transfusion of only red cell concentrates (38%), or plasma (23%). Few MBEs (2%) were treated with coagulation factor concentrates. The effectiveness of the management was assessed as good in significantly larger proportion of MBEs on dabigatran (91%) than on warfarin (84%, odds ratio [OR] 1.68; 95% confidence interval [CI], 1.14-2.49), which was consistent with the lower 30-day mortality (OR (OR 0.66; 95% CI, 0.44-1.00)). The effectiveness of bleeding management in non-traumatic bleeding was better in patients with dabigatran than with warfarin (OR 1.82; 95% CI, 1.18-2.79) but was similar in traumatic bleeding (OR 0.75; 95% CI, 0.25-2.30). The relative effectiveness of management of bleeding and 30-day mortality rates across other key subgroups of patients or sites of bleeding, the use of platelet inhibitors, age-, sex- and renal function subgroups, were comparable in MBEs on dabigatran or warfarin.
  
  
  CONCLUSIONS
  Despite the unavailability of a specific antidote at the time of these studies, bleeding in patients receiving dabigatran was managed in the overwhelming majority of patients without coagulation factor concentrates, with comparable or superior effectiveness and lower 30-day mortality rates versus those who bleed while receiving warfarin.
authors.affiliation: Coagulation Unit, Hematology Center, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Electronic address: ammar.majeed@karolinska.se.
authors.forename: Ammar
authors.initials: A
authors.lastname: Majeed
authors.affiliation: Department of Medicine, Soonchunhyang University Gumi's Hospital, North Kyungsang Province, South Korea.
authors.forename: Hun-Gyu
authors.initials: HG
authors.lastname: Hwang
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada.
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada.
authors.forename: Stuart
authors.initials: S
authors.lastname: Connolly
authors.affiliation: Uppsala Clinical Research Center and Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Feuring
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany; Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Brueckmann
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Noack
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada.
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.affiliation: Coagulation Unit, Hematology Center, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden; Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University and Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada.
authors.forename: Sam
authors.initials: S
authors.lastname: Schulman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D001779:Blood Coagulation Factors / Q000627:therapeutic use; D001803:Blood Transfusion; D000069604:Dabigatran / Q000009:adverse effects* / Q000627:therapeutic use; D019468:Disease Management; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000628:therapy*; D006801:Humans; D008297:Male; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D014859:Warfarin; D000069604:Dabigatran
keywords: Bleeding; Coumarins; Dabigatran etexilate; Management