title: Management of major bleeding events in patients treated with rivaroxaban vs. warfarin: results from the ROCKET AF trial.
abstract: OBJECTIVE
  There are no data regarding management and outcomes of major bleeding events in patients treated with oral factor Xa inhibitors.
  
  
  RESULTS
  Using data from ROCKET AF, we analysed the management and outcomes of major bleeding overall and according to the randomized treatment. During a median follow-up of 1.9 years, 779 (5.5%) patients experienced major bleeding at a rate of 3.52 events/100 patient-years with a similar event rate in each arm (n = 395 rivaroxaban vs. n = 384 warfarin). The median number of transfused packed red blood cells (PRBC) per episode was similar in both arms [2 (25th, 75th: 2, 4) units]. Overall, few transfusions of whole blood (n = 14), platelets (n = 10), or cryoprecipitate (n = 2) were used. Transfusion of fresh frozen plasma (FFP) was significantly less in the rivaroxaban arm (n = 45 vs. n = 81 units) after adjustment for covariates [odds ratio (OR) 0.43 (95% CI 0.29-0.66); P < 0.0001]. Prothrombin complex concentrates (PCC) were administered less in the rivaroxaban arm (n = 4 vs. n = 9). Outcomes after major bleeding, including stroke or non-central nervous system embolism (4.7% rivaroxaban vs. 5.4% warfarin; HR 0.89; 95% CI 0.42-1.88) and all-cause death (20.4% rivaroxaban vs. 26.1% warfarin; HR 0.69, 95% CI 0.46-1.04) were similar in patients treated with rivaroxaban and warfarin (interaction P = 0.51 and 0.11).
  
  
  CONCLUSIONS
  Among high-risk patients with atrial fibrillation who experienced major bleeding in ROCKET AF, the use of FFP and PCC was less among those allocated rivaroxaban compared with warfarin. However, use of PRBCs and outcomes after bleeding were similar among patients randomized to rivaroxaban or to warfarin.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, PO Box 17969, Durham, NC 27710, USA jonathan.piccini@duke.edu.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Piccini
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, PO Box 17969, Durham, NC 27710, USA.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Garg
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, PO Box 17969, Durham, NC 27710, USA.
authors.forename: Manesh R
authors.initials: MR
authors.lastname: Patel
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, PO Box 17969, Durham, NC 27710, USA.
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lokhnygina
authors.affiliation: Canadian Heart Research Centre and Terrence Donnelly Heart Centre, Division of Cardiology, St Michael's Hospital, University of Toronto, Toronto, Canada.
authors.forename: Shaun G
authors.initials: SG
authors.lastname: Goodman
authors.affiliation: Division of Cardiovascular Health and Disease, University of Cincinnati, Cincinnati, OH.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.affiliation: Bayer HealthCare Pharmaceuticals, Montville, NJ, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Berkowitz
authors.affiliation: Hospital of the University of Münster, Münster, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Breithardt
authors.affiliation: Ruprecht-Karls-University, Heidelberg, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Hacke
authors.affiliation: Cardiovascular Institute, Mount Sinai Medical Center, New York, NY, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Halperin
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia, Crawley, Australia.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.affiliation: Janssen Research and Development, Raritan, NJ, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Nessel
authors.affiliation: Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Singer
authors.affiliation: Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.affiliation: University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, UK.
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D000933:Antifibrinolytic Agents / Q000008:administration & dosage; D001281:Atrial Fibrillation / Q000150:complications*; D001803:Blood Transfusion / Q000706:statistics & numerical data; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D065427:Factor Xa Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects*; D010949:Plasma; D000069552:Rivaroxaban; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome; D014812:Vitamin K / Q000008:administration & dosage; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D014812:Vitamin K; D014859:Warfarin; D000069552:Rivaroxaban
keywords: Atrial fibrillation; Bleeding; Factor Xa inhibitor