Written by Millie Cossé
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IV alteplase administered between 4.5 to 24 hours in patients with acute ischemic stroke and salvageable brain tissue on perfusion imaging had significantly improved functional outcomes but increased incidence in symptomatic intracranial hemorrhage.
A New HOPE
This prospective randomized control trial of 372 patients with acute ischemic stroke sought to evaluate the safety of administering IV alteplase 4.5 to 24 hours after the onset of symptoms. Patients across 26 stroke centers in China were enrolled and randomized to either IV alteplase or standard medical therapy. Eligibility included onset time of 4.5 to 24 hours, no initial plans for thrombectomy, and salvageable brain tissue identified on CT perfusion imaging.
As expected, the alteplase group had a higher incidence of symptomatic intracranial hemorrhage (3.8% compared to 0.51% in the standard treatment group, 95% CI 1.54-34.84), but also a substantial increase in functional independence (40% in the alteplase group and 26% in the standard group 95% CI 1.14-2/02, P=0.004). Authors defined functional independence as a modified Rankin Scale score of 0 to 1 at 90 days, which means no symptoms or ability to carry out all usual duties and activities.
How will this change my practice?
This well-done RCT supports extending the window for thrombolytics in select patients with salvageable brain tissue. However, these changes are not without serious risks of increased intracranial bleeding. Additionally, we have to consider the TIMELESS trial, which also examined the effect of Tenecteplase administration in the 4.5 to 24-hour window and did not demonstrate a benefit (although only LVO patients were included). This trial supports extending the therapeutic window for thrombolytics, but it is probably not enough evidence to change stroke protocols.
Source
HOPE investigators. Alteplase for Acute Ischemic Stroke at 4.5 to 24 Hours: The HOPE Randomized Clinical Trial. JAMA. 2025 Sep 2;334(9):788-797. doi: 10.1001/jama.2025.12063. PMID: 40773205; PMCID: PMC12332759.
