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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. CONCLUSION: 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.

Original publication




Journal article


Cerebrovasc Dis

Publication Date





223 - 228


Aged, Aged, 80 and over, Brain Ischemia, Canada, Chi-Square Distribution, Drug Administration Schedule, Female, Fibrinolytic Agents, Humans, Infusions, Intravenous, Intracranial Hemorrhages, Male, Middle Aged, Patient Selection, Prospective Studies, Registries, Regression Analysis, Risk Assessment, Risk Factors, Stroke, Thrombolytic Therapy, Time Factors, Tissue Plasminogen Activator, Treatment Outcome