title: Intracranial hemorrhage among patients with atrial fibrillation anticoagulated with warfarin or rivaroxaban: the 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
  Intracranial hemorrhage (ICH) is a life-threatening complication of anticoagulation.
  
  
  METHODS
  We investigated the rate, outcomes, and predictors of ICH in 14 264 patients with atrial fibrillation from Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Cox proportional hazards modeling was used.
  
  
  RESULTS
  During 1.94 years (median) of follow-up, 172 patients (1.2%) experienced 175 ICH events at a rate of 0.67% per year. The significant, independent predictors of ICH were race (Asian: hazard ratio, 2.02; 95% CI, 1.39-2.94; black: hazard ratio, 3.25; 95% CI, 1.43-7.41), age (1.35; 1.13-1.63 per 10-year increase), reduced serum albumin (1.39; 1.12-1.73 per 0.5 g/dL decrease), reduced platelet count below 210×10(9)/L (1.08; 1.02-1.13 per 10×10(9)/L decrease), previous stroke or transient ischemic attack (1.42; 1.02-1.96), and increased diastolic blood pressure (1.17; 1.01-1.36 per 10 mm Hg increase). Predictors of a reduced risk of ICH were randomization to rivaroxaban (0.60; 0.44-0.82) and history of congestive heart failure (0.65; 0.47-0.89). The ability of the model to discriminate individuals with and without ICH was good (C-index, 0.69; 95% CI, 0.64-0.73).
  
  
  CONCLUSIONS
  Among patients with atrial fibrillation treated with anticoagulation, the risk of ICH was higher among Asians, blacks, the elderly, and in those with previous stroke or transient ischemic attack, increased diastolic blood pressure, and reduced platelet count or serum albumin at baseline. The risk of ICH was significantly lower in patients with heart failure and in those who were randomized to rivaroxaban instead of warfarin. The external validity of these findings requires testing in other atrial fibrillation populations.
authors.affiliation: From the School of Medicine and Pharmacology, The University of Western Australia, Perth, Australia (G.J.H.); Department of Neurology, Sir Charles Gairdner Hospital, Perth, Australia (G.J.H.); Duke Clinical Research Institute (S.R.S., J.P.P., Y.L., M.R.P.) and Duke Translational Medicine Institute (R.M.C.), Duke University Medical Center, Durham, NC; Department of Medicine, Stanford University, CA (K.W.M.); Cardiovascular Institute, Mount Sinai Medical Center, New York (J.L.H.); Department of Cardiovascular Medicine, Hospital of the University of Münster, Münster, Germany (G.B.); Massachusetts General Hospital and Harvard Medical School, Boston (D.E.S.); University of Cincinnati College of Medicine, OH (R.C.B.); Department of Global Clinical Development, Bayer HealthCare Pharmaceuticals, Whippany, NJ (S.D.B.); Cerenis Therapeutics, Labege, France (J.F.P.); Janssen Research and Development, Raritan, NJ (C.C.N.); Ruprecht- Karls-University, Heidelberg, Germany (W.H.); and University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom (K.A.A.F.).
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Stevens
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Piccini
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Lokhnygina
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Halperin
authors.forename: Manesh R
authors.initials: MR
authors.lastname: Patel
authors.forename: Günter
authors.initials: G
authors.lastname: Breithardt
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Singer
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.forename: Scott D
authors.initials: SD
authors.lastname: Berkowitz
authors.forename: John F
authors.initials: JF
authors.lastname: Paolini
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Nessel
authors.forename: Werner
authors.initials: W
authors.lastname: Hacke
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D044466:Asian People / Q000208:ethnology; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D044383:Black People / Q000208:ethnology; D004311:Double-Blind Method; D004617:Embolism / Q000517:prevention & control; D065427:Factor Xa Inhibitors; D005260:Female; D006801:Humans; D020300:Intracranial Hemorrhages / Q000097:blood / Q000139:chemically induced / Q000453:epidemiology* / Q000503:physiopathology; D008297:Male; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects*; D011446:Prospective Studies; D000069552:Rivaroxaban; D020521:Stroke / Q000517:prevention & control; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D014812:Vitamin K; D014859:Warfarin; D000069552:Rivaroxaban
keywords: anticoagulation; atrial fibrillation; intracranial hemorrhage; risk prediction