Written by Peter Liu
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For select patients with posterior ischemic stroke, late alteplase administration between 4.5-24 hours after symptom onset resulted in improved functional independence at 90 days.
4.5 hours isn’t too late for lytics in posterior stroke
For ischemic stroke patients without contraindication, thrombolytic therapy within 4.5 hours of symptom onset remains the primary goal. However, therapy between 4.5-24 hours may still be considered when the initial window is missed. While anterior circulation strokes often require perfusion imaging to guide late thrombolysis, the evidence for posterior circulation strokes remains limited.
The multicenter EXPECTS RCT from China investigated IV alteplase administration 4.5-24 hours post-onset in posterior circulation ischemic stroke patients not undergoing thrombectomy. Among 234 patients, functional independence at 90 days was significantly higher in the alteplase group vs. standard care (89.6% vs. 72.6%; adjusted RR 1.16, 95%CI 1.03-1.30; P = 0.01). Symptomatic intracranial hemorrhage was 1.7% vs. 0.9% (unadjusted RR 1.98, 95%CI 0.18-21.56). Mortality was 5.2% with alteplase and 8.5% with standard care (unadjusted RR 0.61, 95%CI 0.23-1.62). Notably, perfusion imaging was not required to demonstrate salvageable tissue.
Despite growing data, the literature on late thrombolysis remains fairly heterogeneous. A recent international study in a similar population (largely non-Asian) who underwent thrombectomy found no clear benefit. The role of perfusion imaging in posterior circulation strokes also remains unclear. Still, EXPECTS contributes to an expanding body of RCT evidence supporting late thrombolytic therapy within 24 hours of ischemic stroke onset.
How does this change my practice?
It used to be that patients who had symptoms of stroke outside of 4.5 hours were never considered for thrombolytic therapy. However, depending on the location of the stroke, there appear to be opportunities to provide timely interventions outside of this small time window. This added complexity has prompted me to involve stroke experts early and often in my inpatients with acute neurologic symptoms compatible with stroke, even if time of symptom onset is unknown or exceeds 4.5 hours.
Source
Alteplase for Posterior Circulation Ischemic Stroke at 4.5 to 24 Hours. N Engl J Med. 2025 Apr 3;392(13):1288-1296. doi: 10.1056/NEJMoa2413344. PMID: 40174223
