title: Thrombolysis at 3-4.5 hours after acute ischemic stroke onset--evidence from the Canadian Alteplase for Stroke Effectiveness Study (CASES) registry.
abstract: BACKGROUND
  Extending the therapeutic window for thrombolysis is an important strategy in maximizing the proportion of patients treated. ECASS III examined a 3-4.5-hour window and showed a benefit to treated patients. We examined the experience in Canadian centres using intravenous tPA treatment in the 3-4.5-hour time window.
  
  
  METHODS
  The data were obtained from the CASES (Canadian Alteplase for Stroke Effectiveness Study)--a prospective, multicentric cohort study with patient enrollment from 60 centres across Canada over 2.5 years. The 90-day outcome, mortality and symptomatic intracranial hemorrhage of patients thrombolysed between 3 and 4.5 h and within 3 h of symptom onset were compared. A mRS 0-1 (no symptoms at all or no significant disability despite symptoms, able to carry out all usual duties and activities) at 90 days was defined as a favorable outcome.
  
  
  RESULTS
  A total of 1,112 patients with complete data were included. 129 (11.6%) patients received tPA between 3 and 4.5 h of symptom onset and 983 (88.4%) patients received tPA within 3 h. At 90 days, 39.4% of the patients in the 3-4.5-hour treatment group and 36.5% of patients in the under 3-hour treatment group attained a mRS ≤1. There were no differences between the two groups regarding their functional status at 3 months. There was a trend towards higher rate of sICH in the 3-4.5-hour group compared to the 0-3-hour group (7.8 vs. 3.8%, p = 0.06). Similarly there was a trend towards higher rate of deaths in the 3-4.5-hour group compared to the 0-3-hour group (28.4 vs. 21.4%, p = 0.09). A χ(2) test for trend demonstrated a rising proportion of symptomatic ICH in later time windows (p = 0.013). A similar trend (non-significant) was observed for mortality.
  
  
  CONCLUSIONS
  Our study suggests that patients with acute ischemic stroke may be successfully treated with intravenous tPA in the 3-4.5-hour treatment window, but cautions that later time window treatment may result in greater adverse events.
authors.affiliation: Calgary Stroke Program, Department of Clinical Neurosciences, Foothills Medical Center, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Nandavar
authors.initials: N
authors.lastname: Shobha
authors.forename: Alastair M
authors.initials: AM
authors.lastname: Buchan
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hill
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D002170:Canada; D016009:Chi-Square Distribution; D004334:Drug Administration Schedule; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D020300:Intracranial Hemorrhages / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011446:Prospective Studies; D012042:Registries; D012044:Regression Analysis; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000401:mortality; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator