title: Factors associated with major bleeding events: insights from the ROCKET AF trial (rivaroxaban once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation).
abstract: OBJECTIVE
  This study sought to report additional safety results from the ROCKET AF (Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).
  
  
  BACKGROUND
  The ROCKET AF trial demonstrated similar risks of stroke/systemic embolism and major/nonmajor clinically relevant bleeding (principal safety endpoint) with rivaroxaban and warfarin.
  
  
  METHODS
  The risk of the principal safety and component bleeding endpoints with rivaroxaban versus warfarin were compared, and factors associated with major bleeding were examined in a multivariable model.
  
  
  RESULTS
  The principal safety endpoint was similar in the rivaroxaban and warfarin groups (14.9 vs. 14.5 events/100 patient-years; hazard ratio: 1.03; 95% confidence interval: 0.96 to 1.11). Major bleeding risk increased with age, but there were no differences between treatments in each age category (<65, 65 to 74, ≥75 years; pinteraction = 0.59). Compared with those without (n = 13,455), patients with a major bleed (n = 781) were more likely to be older, current/prior smokers, have prior gastrointestinal (GI) bleeding, mild anemia, and a lower calculated creatinine clearance and less likely to be female or have a prior stroke/transient ischemic attack. Increasing age, baseline diastolic blood pressure (DBP) ≥90 mm Hg, history of chronic obstructive pulmonary disease or GI bleeding, prior acetylsalicylic acid use, and anemia were independently associated with major bleeding risk; female sex and DBP <90 mm Hg were associated with a decreased risk.
  
  
  CONCLUSIONS
  Rivaroxaban and warfarin had similar risk for major/nonmajor clinically relevant bleeding. Age, sex, DBP, prior GI bleeding, prior acetylsalicylic acid use, and anemia were associated with the risk of major bleeding. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation: NCT00403767).
authors: Canadian Heart Research Centre and Terrence Donnelly Heart Centre, Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. Electronic address: goodmans@chrc.net.
authors: Shaun G
authors: SG
authors: Goodman
authors: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors: Daniel M
authors: DM
authors: Wojdyla
authors: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors: Jonathan P
authors: JP
authors: Piccini
authors: Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand.
authors: Harvey D
authors: HD
authors: White
authors: Bayer HealthCare Pharmaceuticals, Montville, New Jersey.
authors: John F
authors: JF
authors: Paolini
authors: Janssen Research and Development, Raritan, New Jersey.
authors: Christopher C
authors: CC
authors: Nessel
authors: Bayer HealthCare Pharmaceuticals, Montville, New Jersey.
authors: Scott D
authors: SD
authors: Berkowitz
authors: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors: Kenneth W
authors: KW
authors: Mahaffey
authors: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors: Manesh R
authors: MR
authors: Patel
authors: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors: Matthew W
authors: MW
authors: Sherwood
authors: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors: Richard C
authors: RC
authors: Becker
authors: Cardiovascular Institute, Mount Sinai Medical Center, New York, New York.
authors: Jonathan L
authors: JL
authors: Halperin
authors: Ruprecht-Karls-University, Heidelberg, Germany.
authors: Werner
authors: W
authors: Hacke
authors: Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors: Daniel E
authors: DE
authors: Singer
authors: Royal Perth Hospital, Perth, Australia.
authors: Graeme J
authors: GJ
authors: Hankey
authors: Hospital of the University of Münster, Münster, Germany.
authors: Gunter
authors: G
authors: Breithardt
authors: University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, Scotland, United Kingdom.
authors: Keith A A
authors: KA
authors: Fox
authors: Duke Clinical Research Institute and Duke Translational Medicine Institute, Duke University Medical Center, Durham, North Carolina.
authors: Robert M
authors: RM
authors: Califf
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D001794:Blood Pressure; D004617:Embolism / Q000517:prevention & control*; D065427:Factor Xa Inhibitors; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage*; D061214:Patient Safety; D012307:Risk Factors; D000069552:Rivaroxaban; D020521:Stroke / Q000517:prevention & control*; D013876:Thiophenes / Q000008:administration & dosage*; D013997:Time Factors; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D014859:Warfarin / Q000008:administration & dosage
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D014812:Vitamin K; D014859:Warfarin; D000069552:Rivaroxaban
keywords: anticoagulants; atrial fibrillation; hemorrhage