JAMA. 2025 Oct 13. doi: 10.1001/jama.2025.16876. Online ahead of print.
ABSTRACT
IMPORTANCE: Functional outcomes in patients with acute ischemic stroke due to large-vessel occlusion who undergo thrombectomy remain suboptimal, and the benefits of intra-arterial alteplase after thrombectomy remain uncertain.
OBJECTIVE: To investigate whether treatment with intra-arterial alteplase after successful endovascular reperfusion improves functional outcomes among patients with acute, anterior-circulation, large-vessel occlusion stroke.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter, randomized clinical trial recruited patients with anterior-circulation, large-vessel occlusion stroke within 24 hours of symptom onset who achieved successful reperfusion (expanded Thrombolysis in Cerebral Infarction scale score of ≥2b50) after thrombectomy. Guideline-based intravenous thrombolysis was allowed. Patients were randomized between August 1, 2023, and October 16, 2024, and the trial was conducted at 28 hospitals in China. Final follow-up occurred on January 7, 2025.
INTERVENTIONS: Intra-arterial alteplase treatment (n = 164) with 0.225 mg/kg (maximum dose of 20 mg) vs standard treatment (n = 160).
MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with a modified Rankin Scale score of 0 or 1 at 90 days (score range, 0 [no symptoms] to 6 [death]; a score of 0 or 1 indicates an excellent outcome). The safety outcomes included symptomatic intracranial hemorrhage within 36 hours of randomization, all-cause mortality within 90 days, and any intracranial hemorrhage within 36 hours.
RESULTS: Of the 324 patients randomized (median age, 68 years [IQR, 58-75 years]; 99 were female [30.6%]), 1 patient in each group was lost to follow-up. The proportion of patients with a modified Rankin Scale score of 0 or 1 at 90 days was 44.8% (73/163) in the intra-arterial alteplase group vs 30.2% (48/159) in the standard treatment group (adjusted risk ratio [RR], 1.45 [95% CI, 1.08-1.96]; P = .01). The proportion of patients with symptomatic intracranial hemorrhage within 36 hours was 4.3% (7/164) in the intra-arterial alteplase group vs 5.0% (8/160) in the standard treatment group (adjusted RR, 0.85 [95% CI, 0.43-1.69]; P = .67). The proportion of patients with all-cause mortality within 90 days was 17.1% (28/164) in the intra-arterial alteplase group vs 11.3% (18/160) in the standard treatment group (adjusted hazard ratio, 1.60 [95% CI, 0.88-2.89]; P = .12). The proportion of patients with any intracranial hemorrhage within 36 hours was 32.9% (54/164) in the intra-arterial alteplase group vs 26.9% (43/160) in the standard treatment group (adjusted RR, 1.22 [95% CI, 0.92-1.63]; P = .17).
CONCLUSIONS AND RELEVANCE: Among patients with acute, anterior-circulation, large-vessel occlusion stroke who achieved successful endovascular reperfusion by mechanical thrombectomy, intra-arterial alteplase resulted in a higher likelihood of excellent outcomes at 90 days. The incidence of all-cause mortality and any intracranial hemorrhage was higher in patients who received intra-arterial alteplase, although these differences were not statistically significant.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05856851.
PMID:42262770 | DOI:10.1001/jama.2025.16876
