Background: Intravenous thrombolysis with alteplase 3 to 4.5 hours after ischemic stroke onset has been proved by a randomized trial and recommended by several guidelines. However, it is still an off-label treatment in many countries, including Taiwan. The present study aimed to investigate the effectiveness and safety of alteplase administered between 3 and 4.5 hours after stroke onset by a retrospective observational study.
Methods: Multi-center stroke registry has been well undertaken in Taiwan since 2006. Based on Taiwan Stroke Registry, we included ischemic stroke patients who received intravenous thrombolysis with alteplase 3 to 4.5 hours after onset of a stroke into analysis. Patients who received superimposed endovascular treatment, or enrolled in acute stroke treatment trials were excluded. Age-and-sex matched controls were also selected as the following criteria: onset to hospital arrival 2-4.5 hours, no absolute contraindication for thrombolytic therapy, and no use of any thrombolytic agents or endovascular treatment. The effectiveness was evaluated by a favorable outcome at 3 months, modified Rankin scale 0 or 1, and safety was determined by symptomatic intracranial hemorrhage (ICH) and mortality at 3 months.
Results: A total of 748 patients were recruited from 16 hospitals, including 374 (67% men, mean age, 67.8+12.5 years) in the alteplase group and 374 (67% men, mean age, 66.1+13.2 years) in the control group. Patients in the alteplase group had more favorable outcome than in the control group (34.0% vs. 22.7%; odds ratio [OR], 1.75; 95% confidence interval [CI], 1.27-2.42; P=0.001). There was no significant difference of symptomatic ICH (alteplase, 5.6% vs. control 2.9%, OR, 1.96; 95% CI, 0.93-4.13; P=0.076), and mortality (alteplase, 7.8% vs. control 7.5%; OR, 1.04; 95% CI, 0.61-1.78; P=0.89) between two groups. Compared to patients received standard dose of alteplase (n=182), those with reduced dose of alteplase (n=192) did not have lower hemorrhagic transformation and better functional outcome.
Conclusion: The effectiveness and safety of intravenous alteplase administration 3 to 4.5 hours after stroke onset was confirmed in this retrospective analysis in Taiwan.

Intravenous Thrombolysis at 3-4.5 Hours After Acute Ischemic Stroke: A Retrospective Multi-center Observational Study in Taiwan