Daily Literature Update
Alteplase for Posterior Circulation Ischemic Stroke at 4.5 to 24 Hours
Yan S, Zhou Y, Lansberg MG, et al. Alteplase for Posterior Circulation Ischemic Stroke at 4.5 to 24 Hours. N Engl J Med. 2025;392(13):1288-1296. doi:10.1056/NEJMoa2413344. PMID:40174223.
Introduction
IV alteplase 4.5 to 24 hours post-stroke improves functional independence in mild posterior circulation ischemic stroke patients in a Chinese cohort.
Study Type: Randomized controlled trial
Population: 234 mild posterior circulation stroke patients (median NIHSS 3)
Intervention: IV alteplase 0.9 mg/kg from 4.5 to 24 hours post onset
Outcomes: Functional independence at 90 days, safety (ICH, death)
Key Findings
- 89.6% functional independence with alteplase vs 72.6% standard care
- Adjusted risk ratio 1.16 (95% CI, 1.03–1.30), P=0.01
- Low symptomatic ICH: 1.7% vs 0.9%
- Lower 90-day mortality: 5.2% vs 8.5%
Context & Related Research
- Yan et al., 2025: RCT showing significant functional benefit and safety in extended window posterior circulation stroke (PMID:40174223), landmark evidence for clinical practice.
- TIMS-China registry, 2016: Observational data confirming safety and efficacy of IV alteplase within 4.5 hrs in idiopathic posterior circulation stroke (PMID:27310965), foundational benchmark.
- Yang et al., 2016: Prospective cohort supporting favorable 90-day outcomes and hemorrhage rates in posterior circulation stroke (PMID:27418829), adding population-specific validation.
- Li et al., 2024: Predictive modeling study aiding in identifying patients likely to benefit from thrombolysis (PMID:38862629), enhancing patient selection strategies.
Clinical Implications
- Expand consideration of IV alteplase to 4.5–24 h window in mild posterior circulation strokes not eligible for thrombectomy.
- Expect improved functional outcomes with low symptomatic hemorrhage risk.
- Utilize predictive tools and clinical judgment to optimize patient selection.
Strengths & Limitations
| Strengths | Limitations |
|---|---|
| Randomized controlled design focused on extended treatment window | Limited to mild stroke severity; excludes thrombectomy candidates |
| Comprehensive safety monitoring; population-specific insights | Study population exclusively Chinese; generalizability uncertain |
Future Directions
Further trials are needed to assess alteplase use beyond 24 hours, in severe strokes, diverse populations, and versus thrombectomy in posterior circulation ischemic stroke.
Conclusion
Intravenous alteplase administered 4.5 to 24 hours post-stroke significantly improves functional independence at 90 days in selected mild posterior circulation stroke patients with low hemorrhagic risk.
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Citations
- Yan S, Zhou Y, Lansberg MG, et al. Alteplase for Posterior Circulation Ischemic Stroke at 4.5 to 24 Hours. N Engl J Med. 2025;392(13):1288-1296. doi:10.1056/NEJMoa2413344. PMID:40174223.
- Chen WH, Zhao XQ, et al. TIMS-China registry: safety and efficacy of IV alteplase within 4.5 hours in posterior circulation stroke. Stroke. 2016; PMID:27310965.
- Yang J, Xu Y, et al. Prospective cohort outcomes in posterior circulation stroke. Neurology. 2016; PMID:27418829.
- Li X, Wang Y, et al. Predictive models for thrombolysis benefit in stroke. J Stroke Cerebrovasc Dis. 2024; PMID:38862629.
