title: Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: the RE-LY trial.
abstract: OBJECTIVE
  Intracranial hemorrhage is the most devastating complication of anticoagulation. Outcomes associated with different sites of intracranial bleeding occurring with warfarin versus dabigatran have not been defined.
  
  
  METHODS
  Analysis of 18 113 participants with atrial fibrillation in the Randomized Evaluation of Long-term anticoagulant therapY (RE-LY) trial assigned to adjusted-dose warfarin (target international normalized ratio, 2-3) or dabigatran (150 mg or 110 mg, both twice daily).
  
  
  RESULTS
  During a mean of 2.0 years of follow-up, 154 intracranial hemorrhages occurred in 153 participants: 46% intracerebral (49% mortality), 45% subdural (24% mortality), and 8% subarachnoid (31% mortality). The rates of intracranial hemorrhage were 0.76%, 0.31%, and 0.23% per year among those assigned to warfarin, dabigatran 150 mg, and dabigatran 110 mg, respectively (P<0.001 for either dabigatran dose versus warfarin). Fewer fatal intracranial hemorrhages occurred among those assigned dabigatran 150 mg and 110 mg (n=13 and n=11, respectively) versus warfarin (n=32; P<0.01 for both). Fewer traumatic intracranial hemorrhages occurred among those assigned to dabigatran (11 patients with each dose) compared with warfarin (24 patients; P<0.05 for both dabigatran doses versus warfarin). Independent predictors of intracranial hemorrhage were assignment to warfarin (relative risk, 2.9; P<0.001), aspirin use (relative risk, 1.6; P=0.01), age (relative risk, 1.1 per year; P<0.001), and previous stroke/transient ischemic attack (relative risk, 1.8; P=0.001).
  
  
  CONCLUSIONS
  The clinical spectrum of intracranial hemorrhage was similar for patients given warfarin and dabigatran. Absolute rates at all sites and both fatal and traumatic intracranial hemorrhages were lower with dabigatran than with warfarin. Concomitant aspirin use was the most important modifiable independent risk factor for intracranial hemorrhage.
authors.affiliation: Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada. robert.hart@phri.ca
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hart
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Diener
authors.forename: Sean
authors.initials: S
authors.lastname: Yang
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Connolly
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.forename: Paul A
authors.initials: PA
authors.lastname: Reilly
authors.forename: Michael D
authors.initials: MD
authors.lastname: Ezekowitz
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
mesh_terms: D000368:Aged; D000925:Anticoagulants; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D000069604:Dabigatran; D005260:Female; D006801:Humans; D019934:International Normalized Ratio / Q000009:adverse effects; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000401:mortality; D008297:Male; D011859:Radiography; D012307:Risk Factors; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects*; D015091:beta-Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000925:Anticoagulants; D001562:Benzimidazoles; D015091:beta-Alanine; D014859:Warfarin; D000069604:Dabigatran