Citation: Yan S, et al. Alteplase for Posterior Circulation Ischemic Stroke at 4.5 to 24 Hours. The New England Journal of Medicine. 2025 Apr 3;392(13):1288-1296. doi: 10.1056/NEJMoa2413344.

Background

Intravenous alteplase is well established for acute ischemic stroke within 4.5 hours of symptom onset, but its efficacy and safety in the extended window (4.5–24 hours) for posterior circulation strokes remain uncertain. Posterior circulation strokes, including basilar artery occlusion, comprise 15%-20% of ischemic strokes and often present with variable and or mild symptoms.¹ Because the brainstem and cerebellum receive robust collateral flow through perforating branches of the basilar artery, these regions are relatively more resistant to ischemia, and the risk of hemorrhagic transformation after IV thrombolysis is lower than in anterior circulation strokes.² Most prior trials have focused on anterior circulation strokes or relied on advanced imaging selection, leaving limited evidence for late-window thrombolysis in posterior circulation strokes without planned thrombectomy.

Methods

EXPECTS was a prospective, randomized, outcome-blinded trial conducted across 30 stroke centers in China. Adults ≥18 years old with MRI- or CT-confirmed posterior circulation stroke were eligible if they had a PC-ASPECTS of > 7 on non-contrast CT (even if < 7 on diffusion-weighted imaging), a NIHSS > 1, and a pre-stroke mRS of 0-1. Participants were randomized 1:1 to receive alteplase (0.9mg/kg) or standard medical therapy. Exclusion criteria included planned thrombectomy or contraindication to alteplase.

The primary outcome was functional independence (mRS score of 0-2 at 90 days). Secondary outcomes included absence of disability (mRS 0-1 at 90 days) and neurological improvement (NIHSS reduction ≥ 8 points or score ≤ 1) at 24 hours and 7 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH, defined as an increase in NIHSS ≥ 4 points with imaging evidence), parenchymal hematoma, and any intracranial hemorrhage within 36 hours, as well as all-cause mortality within 90 days. Analyses were intention-to-treat basis, adjusted for age, baseline NIHSS, and time from onset to randomization, using ordinal logistic regression for mRS distribution.

Results

A total of 234 patients were enrolled—117 assigned to alteplase and 117 to standard medical therapy. Among those receiving standard therapy, 43.5% received single and 56.5% dual antiplatelet therapy. Median age was 64 years (IQR 55-74), and the median baseline NIHSS score was 3 (IQR 2-6), indicating mostly mild strokes. Posterior circulation infarcts were MRI-confirmed in 61.5% of patients.

At 90 days, functional independence was achieved in 89.6% of the alteplase group versus 72.6% in the standard treatment group (adjusted risk ratio, 1.16; 95% CI, 1.03-1.30; p=0.01). Secondary outcomes similarly favored alteplase, with an adjusted common odds ratio for global functional improvement of 2.12 (95% CI 1.31–3.43). Absence of disability (mRS 0–1) occurred in 73.9% versus 60.7% (adjusted RR 1.16; 95% CI 0.98–1.36). Adjustments for multiple comparisons were not applied, so secondary outcomes should be interpreted as exploratory.

Adverse events were infrequent, and rates were comparable between groups. The incidence of sICH within 36 hours was low (1.7% alteplase vs. 0.9% standard care). Parenchymal hematoma occurred in 2.6% and 0.9%, respectively, while any intracranial hemorrhage within 36 hours was seen in 9.5% versus 4.3%. Ninety-day all-cause mortality was 5.2% in the alteplase group compared with 8.5% in the control group. Although hemorrhagic events were numerically higher with alteplase, absolute rates were low, and confidence intervals were wide due to small event numbers, limiting firm conclusions about safety.

Commentary

This multicenter, prospective, randomized trial provides the strongest evidence to date supporting thrombolysis beyond 4.5 hours in posterior circulation stroke. Alteplase administered 4.5-24 hours after onset improved functional outcomes at 90 days without a statistically significant increase in hemorrhage or mortality.

The trial population was predominantly comprised of mild strokes and excluded those with planned thrombectomy, limiting generalizability to more severe cases. Additional limitations include the exclusive conduct of the trial in China, use of non-contrast CT rather than MRI or perfusion imaging, and the open-label design, which introduces potential bias. Nonetheless, these results align with emerging evidence that posterior circulation strokes may tolerate delayed reperfusion better than anterior circulation strokes and carry a low hemorrhagic risk.

Impact on Clinical Practice:

EXPECTS suggests that carefully selected patients with mild posterior circulation ischemic stroke may benefit from IV alteplase up to 24 hours after onset when thrombectomy is not indicated or feasible. In practice, this could broaden the therapeutic window in resource-limited or transfer settings where advanced imaging or endovascular access is delayed.

While confirmatory trials in more diverse populations are needed, EXPECTS reinforces a growing shift toward individualized reperfusion decisions—balancing tissue viability, infarct location, and hemorrhagic risk—rather than rigid adherence to time-based cutoffs.

References

1. Novakovic-White R, Corona JM, White JA. Posterior Circulation Ischemia in the Endovascular Era. Neurology. 2021 Nov 16;97(20 Suppl 2):S158-S169.

2. Lee S-H, Han JH, Jung I, Jung J-M. Do thrombolysis outcomes differ between anterior circulation stroke and posterior circulation stroke? A systematic review and meta-analysis. Int J Stroke 2020;15:849-57.