PDF: EXPECTS
(2025)Objective
Efficacy and safety of IV tPA administered 4.5 to 24 hours from onset in patients with posterior circulation stroke who were not candidates for thrombectomy.
Study Summary
• sICH within 36 hours was rare and similar between groups (1.7% vs 0.9%).
• 90-day mortality was lower with alteplase but non-significant (5.2% vs 8.5%).
Intervention
Alteplase (0.9 mg/kg, max 90 mg) vs. standard medical care, administered between 4.5 to 24 hours post onset.
Inclusion Criteria
Age ≥18, clinical signs of posterior circulation stroke confirmed by imaging (DWI, CT), PC-ASPECTS ≥7, NIHSS ≥1, pre-stroke mRS 0–1, no extensive early ischemic changes, no thrombectomy planned.
Study Design
Arms: Alteplase 0.9mg/kg (n=117) vs Standard Medical Treatment (n=117)
Patients per Arm: Alteplase: 117, Standard Treatment: 117
Outcome
• mRS 0–1 at 90 days: 73.9% vs 60.7%
• sICH within 36 hours: 1.7% vs 0.9%
• 90-day mortality: 5.2% vs 8.5%
Bottom Line
In Chinese patients with mainly mild posterior circulation ischemic stroke who did not receive thrombectomy, alteplase administered 4.5 to 24 hours after stroke onset resulted in a higher frequency of functional independence at 90 days compared to standard medical care, with similar rates of symptomatic intracranial hemorrhage and lower mortality.
Major Points
- 234 patients were enrolled (117 alteplase, 117 standard treatment).
- A higher percentage of patients in the alteplase group achieved functional independence (mRS 0-2) at 90 days compared to the standard treatment group (89.6% vs. 72.6%; adjusted risk ratio, 1.16; 95% CI, 1.03 to 1.30; P=0.01).
- The median NIHSS score at randomization was 3 (IQR 2-6), indicating mostly mild strokes.
- The incidence of symptomatic intracranial hemorrhage within 36 hours was 1.7% in the alteplase group and 0.9% in the standard treatment group (unadjusted risk ratio, 1.98; 95% CI, 0.18 to 21.56).
- At 90 days, 5.2% of alteplase patients and 8.5% of standard treatment patients had died (unadjusted risk ratio, 0.61; 95% CI, 0.23 to 1.62).
- An ordinal analysis of mRS distribution showed functional improvement with an adjusted common odds ratio of 2.12 (95% CI, 1.31 to 3.43) favoring alteplase.
- Patients with planned thrombectomy were excluded, limiting generalizability to more severe strokes.
Study Design
- Study Type
- Prospective, multicenter, open-label, randomized trial with blinded outcome assessment
- Randomization
- Yes
- Blinding
- Blinded outcome assessment by trained third-party personnel.
- Sample Size
- 234
- Follow-up
- 90 days
- Centers
- 30
- Countries
- China
Primary Outcome
Definition: Functional independence, defined as a score of 0 to 2 on the modified Rankin scale, at 90 days.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 85 of 117 patients (72.6%) | 103 of 115 patients (89.6%) | 1.16 (1.03-1.30) | 0.01 |
Limitations & Criticisms
- The trial excluded patients with planned thrombectomy, limiting generalizability to patients presenting directly to thrombectomy-capable centers or with more severe strokes.
- The trial population primarily included patients with mild strokes, which may limit the generalizability to patients with more severe posterior circulation strokes.
- The use of alteplase was based on established efficacy at trial initiation, but future studies should explore tenecteplase for simplified administration and potential benefits.
Citation
N Engl J Med 2025;392:1288-96.