title: Gastrointestinal Bleeding in Patients With Atrial Fibrillation Treated With Rivaroxaban or Warfarin: ROCKET AF Trial.
abstract: BACKGROUND
  Gastrointestinal (GI) bleeding is a common complication of oral anticoagulation.
  
  
  OBJECTIVE
  This study evaluated GI bleeding in patients who received at least 1 dose of the study drug in the on-treatment arm of 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) trial.
  
  
  METHODS
  The primary outcome was adjudicated GI bleeding reported from first to last drug dose + 2 days. Multivariable modeling was performed with pre-specified candidate predictors.
  
  
  RESULTS
  Of 14,236 patients, 684 experienced GI bleeding during follow-up. These patients were older (median age 75 years vs. 73 years) and less often female. GI bleeding events occurred in the upper GI tract (48%), lower GI tract (23%), and rectum (29%) without differences between treatment arms. There was a significantly higher rate of major or nonmajor clinical GI bleeding in rivaroxaban- versus warfarin-treated patients (3.61 events/100 patient-years vs. 2.60 events/100 patient-years; hazard ratio: 1.42; 95% confidence interval: 1.22 to 1.66). Severe GI bleeding rates were similar between treatment arms (0.47 events/100 patient-years vs. 0.41 events/100 patient-years; p = 0.39; 0.01 events/100 patient-years vs. 0.04 events/100 patient-years; p = 0.15, respectively), and fatal GI bleeding events were rare (0.01 events/100 patient-years vs. 0.04 events/100 patient-years; 1 fatal events vs. 5 fatal events total). Independent clinical factors most strongly associated with GI bleeding were baseline anemia, history of GI bleeding, and long-term aspirin use.
  
  
  CONCLUSIONS
  In the ROCKET AF trial, rivaroxaban increased GI bleeding compared with warfarin. The absolute fatality rate from GI bleeding was low and similar in both treatment arms. Our results further illustrate the need for minimizing modifiable risk factors for GI bleeding in patients on oral anticoagulation.
authors.affiliation: Division of Cardiovascular Medicine, Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina. Electronic address: matthew.sherwood@dm.duke.edu.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Sherwood
authors.affiliation: Janssen Pharmaceutical Research and Development, Raritan, New Jersey.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Nessel
authors.affiliation: Division of Cardiovascular Medicine, Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Hellkamp
authors.affiliation: Department of Medicine, Stanford University Medical Center, Stanford, California.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Division of Cardiovascular Medicine, Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Piccini
authors.affiliation: Janssen Pharmaceutical Research and Development, Raritan, New Jersey.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Suh
authors.affiliation: Division of Cardiovascular Medicine, Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.affiliation: Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Singer
authors.affiliation: Cardiovascular Institute, Mount Sinai Medical Center, New York, New York.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Halperin
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.affiliation: Bayer HealthCare Pharmaceuticals, Montville, New Jersey.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Berkowitz
authors.affiliation: Department of Medicine, University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Keith A A
authors.initials: KAA
authors.lastname: Fox
authors.affiliation: Division of Cardiovascular Medicine, Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Manesh R
authors.initials: MR
authors.lastname: Patel
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy*; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000175:diagnosis*; D006801:Humans; D038622:Internationality; D008297:Male; D000069552:Rivaroxaban / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D000069552:Rivaroxaban
keywords: anticoagulant; atrial fibrillation; gastrointestinal bleeding; hemorrhage; risk stratification