title: Incidence and Determinants of Traumatic Intracranial Bleeding Among Older Veterans Receiving Warfarin for Atrial Fibrillation.
abstract: Traumatic intracranial bleeding, which is most commonly attributable to falls, is a common concern among health care professionals, who are hesitant to prescribe oral anticoagulants to older adults with atrial fibrillation.
  
  
  
  To describe the incidence of and risk factors for traumatic intracranial bleeding in a large cohort of older adults who were newly prescribed warfarin sodium.
  
  
  
  Retrospective cohort study at the US Department of Veterans Affairs (VA). Participants included 31 951 veterans with atrial fibrillation 75 years or older who were new referrals to VA anticoagulation clinics (for warfarin therapy) between January 1, 2002, and December 31, 2012. The dates of the core analysis were March 2014 through May 2015, and subsequent ad hoc analyses were performed through December 2015. Patients with comorbid conditions requiring warfarin were excluded.
  
  
  
  The primary outcome was hospitalization for traumatic intracranial bleeding. Secondary outcomes included hospitalization for any intracranial bleeding or ischemic stroke. We used International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify the incidence rates of these outcomes after warfarin initiation using VA administrative data (in-system hospitalizations) and Medicare fee-for-service claims data (out-of-system hospitalizations). Clinical characteristics, laboratory results, and pharmacy data were extracted from the VA electronic medical record. For traumatic intracranial bleeding, Cox proportional hazards regression was used to determine predictors of interest selected a priori based on prior known associations.
  
  
  
  The study population comprised 31 951 participants. The mean (SD) patient age was 81.1 (4.1) years, and 98.1% were male. Comorbidities were common, including hypertension (82.5%), coronary artery disease (42.6%), and diabetes mellitus (33.8%). During the study period, the incidence rate of hospitalization for traumatic intracranial bleeding was 4.80 per 1000 person-years. In unadjusted models, significant predictors of traumatic intracranial bleeding included dementia, fall within the past year, anemia, depression, abnormal renal or liver function, anticonvulsant use, labile international normalized ratio, and antihypertensive use. After adjusting for potential confounders, the remaining significant predictors for traumatic intracranial bleeding were dementia (hazard ratio [HR], 1.76; 95% CI, 1.26-2.46), anemia (HR, 1.23; 95% CI, 1.00-1.52), depression (HR, 1.30; 95% CI, 1.05-1.61), anticonvulsant use (HR, 1.35; 95% CI, 1.04-1.75), and labile international normalized ratio (HR, 1.33; 95% CI, 1.04-1.72). The incidence rates of hospitalization for any intracranial bleeding and ischemic stroke were 14.58 and 13.44, respectively, per 1000 person-years.
  
  
  
  Among patients 75 years or older with atrial fibrillation initiating warfarin therapy, the risk factors for traumatic intracranial bleeding are unique from those for ischemic stroke. The high overall rate of intracranial bleeding in our sample supports the need to more systematically evaluate the benefits and harms of warfarin therapy in older adults.
authors.affiliation: Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York2Veterans Affairs New York Harbor Healthcare System, New York.
authors.forename: John A
authors.initials: JA
authors.lastname: Dodson
authors.affiliation: Massachusetts Veterans Epidemiology Research and Information Center, Veterans Affairs Boston Healthcare System, Boston.
authors.forename: Andrew
authors.initials: A
authors.lastname: Petrone
authors.affiliation: Massachusetts Veterans Epidemiology Research and Information Center, Veterans Affairs Boston Healthcare System, Boston4Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
authors.forename: David R
authors.initials: DR
authors.lastname: Gagnon
authors.affiliation: Section of Geriatrics, Department of Medicine, Yale School of Medicine, New Haven, Connecticut6Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Tinetti
authors.affiliation: Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut8Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Connecticut9Robert Wood Johnson Foundation Clinical Schol.
authors.forename: Harlan M
authors.initials: HM
authors.lastname: Krumholz
authors.affiliation: Massachusetts Veterans Epidemiology Research and Information Center, Veterans Affairs Boston Healthcare System, Boston11Division of Aging, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston Massachusetts.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Gaziano
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000188:drug therapy*; D015331:Cohort Studies; D000075203:Contraindications, Drug; D005260:Female; D006801:Humans; D020300:Intracranial Hemorrhages / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology*; D008297:Male; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D014728:Veterans; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D014859:Warfarin