title: Subtherapeutic warfarin is not associated with increased hemorrhage rates in ischemic strokes treated with tissue plasminogen activator.
abstract: OBJECTIVE
  Concern exists that preadmission warfarin use may be associated with an increased risk of intracerebral hemorrhage in patients with ischemic stroke receiving intravenous tissue plasminogen activator, even in those with an international normalized ratio <1.7. However, evidence to date has been derived from a small single-center cohort of patients.
  
  
  METHODS
  We used data from Phase 3 of the Registry of the Canadian Stroke Network. We compared the rates of post-tissue plasminogen activator hemorrhage, including any intracerebral hemorrhage, symptomatic intracerebral hemorrhage, and gastrointestinal hemorrhage in patients with and without preadmission warfarin use. For those receiving warfarin, we restricted the analysis to patients with an international normalized ratio <1.7 on presentation. Secondary outcomes included functional status and mortality. Multivariate analyses were performed to adjust for other prognostic factors.
  
  
  RESULTS
  Our cohort included 1739 patients with acute ischemic stroke treated with intravenous tissue plasminogen activator of whom 125 (7.2%) were receiving warfarin before admission and had an international normalized ratio <1.7. Preadmission warfarin use was not associated with any secondary intracerebral hemorrhage (OR, 1.2; 95% CI, 0.7 to 2.2), symptomatic intracerebral hemorrhage (OR, 1.1; 95% CI, 0.5 to 2.3), or gastrointestinal hemorrhage (OR, 1.1; 95% CI, 0.2 to 5.6). Multivariate analysis showed that preadmission warfarin use was independently associated with a reduced risk of poor functional outcome (OR, 0.6; 95 CI, 0.3 to 0.9), but not with in-hospital mortality (OR, 0.6; 95% CI, 0.3 to 1.0).
  
  
  CONCLUSIONS
  The results from the present study suggest that tissue plasminogen activator treatment appears to be safe in patients with acute ischemic stroke taking warfarin with an international normalized ratio <1.7 and may reduce the risk of poor functional outcome.
authors.affiliation: University of Toronto, Toronto Western Hospital, Department of Medicine, Division of Neurology, 399 Bathurst Street, 5th Floor, West Wing, room 443, Toronto, Ontario M5T 2S8, Canada. m.d.vergouwen@amc.uva.nl
authors.forename: Mervyn D I
authors.initials: MD
authors.lastname: Vergouwen
authors.forename: Leanne K
authors.initials: LK
authors.lastname: Casaubon
authors.forename: Richard H
authors.initials: RH
authors.lastname: Swartz
authors.forename: Jiming
authors.initials: J
authors.lastname: Fang
authors.forename: Melissa
authors.initials: M
authors.lastname: Stamplecoski
authors.forename: Moira K
authors.initials: MK
authors.lastname: Kapral
authors.forename: Frank L
authors.initials: FL
authors.lastname: Silver
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000401:mortality / Q000503:physiopathology; D015331:Cohort Studies; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D014859:Warfarin; D010959:Tissue Plasminogen Activator