title: Effect of warfarin on intracranial hemorrhage incidence and fatal outcomes.
abstract: BACKGROUND
  Avoiding intracranial hemorrhage (ICH) during warfarin therapy is critical but little is known about factors that affect warfarin-related ICH outcomes. We aimed to define the impact of warfarin on ICH incidence rates and to identify baseline clinical characteristics of patients who experienced ICH and factors associated with fatal ICH.
  
  
  METHODS
  The primary outcome of this retrospective cohort study was the incident ICH rate per 10,000 person-years for patients receiving and not receiving warfarin therapy. Cox proportional hazards modeling was used to adjust for potential confounding factors in assessment of the association of warfarin with fatal ICH.
  
  
  RESULTS
  A total of 1348 patients with incident ICH, 259 (19%) who were receiving warfarin therapy, were included. The incident ICH rates were 74/10,000 (warfarin) and 5/10,000 (non-warfarin) person-years (p<0.001). Warfarin patients were older and carried a higher burden of chronic disease. The unadjusted hazard ratio (HR) for fatal ICH was 1.64 (95% confidence interval [CI] 1.31-2.05) for warfarin patients compared to non-warfarin patients. However, the HR was no longer significant after adjustment for confounding variables (1.10; 95% CI 0.84-1.42). An INR greater than 3.5 at presentation doubled the adjusted risk for fatal ICH with warfarin therapy. Subarachnoid and subdural ICHs were less likely to be fatal than other ICH types, and each year increase in age was associated with 4% increased risk of fatal ICH.
  
  
  CONCLUSIONS
  Although warfarin use increases the rate of incident ICH, other factors impact the risk of fatal ICH, even among anticoagulated patients.
authors: Kaiser Permanente Colorado, Aurora, CO; University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Denver, CO. Electronic address: dan.m.witt@kp.org.
authors: Daniel M
authors: DM
authors: Witt
authors: Kaiser Permanente Colorado, Aurora, CO; University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Denver, CO.
authors: Thomas
authors: T
authors: Delate
authors: Boston University School of Medicine, Boston, MA.
authors: Elaine M
authors: EM
authors: Hylek
authors: Kaiser Permanente Colorado, Aurora, CO; University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Denver, CO.
authors: Nathan P
authors: NP
authors: Clark
authors: McMaster University, Hamilton, Canada.
authors: Mark A
authors: MA
authors: Crowther
authors: University of Insubria, Varese, Italy.
authors: Francesco
authors: F
authors: Dentali
authors: University of Insubria, Varese, Italy.
authors: Walter
authors: W
authors: Ageno
authors: Kaiser Permanente Colorado, Aurora, CO.
authors: Kerri D
authors: KD
authors: Martinez
authors: University of Washington, Seattle, WA.
authors: David A
authors: DA
authors: Garcia
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D003120:Colorado / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D020300:Intracranial Hemorrhages / Q000139:chemically induced* / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: Anticoagulants; CDS; CI; CPAAS; Chronic disease score; Clinical Pharmacy Anticoagulation and Anemia Service; Confidence interval; Emergency Treatment; HR; Hazard ratio; ICD-9; ICH; INR; International Classification of Diseases, Ninth Edition; International normalized ratio; Intracerebral Hemorrhages; Intracranial hemorrhage; KPCO; Kaiser Permanente Colorado; Risk Factors; Stroke; Warfarin