Thrombolytic therapy for acute ischemic stroke beyond three hours

Background: Ischemic cerebrovascular accidents remain a leading cause of morbidity and mortality. Thrombolytic therapy for acute ischemic stroke within 3 h of symptom onset of highly select patients has been advocated by some groups since 1995, but trials have yielded inconsistent outcomes. One recent trial demonstrated significant improvement when the therapeutic window was extended to 4.5 h. Clinical Question: Does the intravenous systemic administration of tPA within 4.5 h to select patients with acute ischemic stroke improve functional outcomes? Evidence Review: All randomized controlled trials enrolling patients within 4.5 h were identified, in addition to a meta-analysis of these trial data. Results: The National Institute of Neurological Disorders and Stroke (NINDS) and European Cooperative Acute Stroke Study III (ECASS III) clinical trials demonstrated significantly improved outcomes at 3 months, with increased rates of intracranial hemorrhage, whereas ECASS II and the Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study showed increased hemorrhagic complications without improving outcomes. Meta-analysis of trial data from all ECASS trials, NINDS, and ATLANTIS suggest that thrombolysis within 4.5 h improves functional outcomes. Conclusion: Ischemic stroke tPA treatment within 4.5 h seems to improve functional outcomes and increases symptomatic intracranial hemorrhage rates without significantly increasing mortality.