CanadiEM MVP Infographic Series – Thrombolysis with Alteplase 3 to 4.5 Hours After Acute Ischemic Stroke

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As part of the MVP Infographic Series this post explores “Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke” published by Hacke et al 2008.1

Alteplase is a tissue plasminogen activator used for intravenous thrombolysis treatment of acute ischemic strokes. Prior to this study, Alteplase was only approved until 3hrs following stroke symptom onset. The authors sought to assess the efficacy and the rates of adverse events including haemorrhage of Alteplase at longer intervals.

As described in the infographic, this study was designed as a double blind, multi-site RCT. Patients received a CT (or MRI) prior to randomization. Patients 18-80 years old with acute ischemic stroke and who were able to receive the study drug were included. Patients with intracranial hemorrhage or severe stroke were excluded. The treatment group of 418 patients received 0.9 mg/kg of Alteplase while the control group received placebo.

It was found that in the treatment group, while Alteplase given at 3 to 4.5 hours after the onset of acute stroke symptoms increases the incidence of symptomatic intracranial hemorrhage, it decreased disability in the study population. There was no difference in mortality between the groups.

This study was instrumental in extending the thrombolysis treatment window for ischemic strokes. However, as this is an older study, it needs to be interpreted in the context of newer interventions for strokes such as endovascular thrombectomy intervention that can be performed up to 24hrs post symptoms.2



Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317-1329. [PubMed]
Powers W, Rabinstein A, Ackerson T, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46-e110. [PubMed]

Amy Chung

Amy is a first year Family Medicine resident at the University of Ottawa. She is interested in efficient knowledge synthesis, technology, and procedural skills. Outside of the hospital, she enjoys long-distance running, and hiking.
Alvin is currently a PGY5 in the FRCP EM program at McMaster University. He serves as Director of Design for CanadiEM and has interests in knowledge translation and health innovation.