Dose-Specific Intra-Arterial Thrombolysis After Endovascular Thrombectomy for Large-Vessel Occlusion Stroke: A...

Randomized trials evaluating adjunctive intra-arterial (IA) thrombolysis after endovascular thrombectomy (EVT) for large-vessel occlusion acute ischemic stroke have recently emerged, and the optimal agent and dose remain uncertain. We compared the efficacy and safety of dose-specific IA thrombolysis regimens following successful EVT.

We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to October 30, 2025, for randomized controlled trials enrolling adults with large-vessel occlusion acute ischemic stroke who achieved angiographic reperfusion after EVT and were randomized to adjunctive IA alteplase, tenecteplase, or urokinase versus EVT alone. We performed a frequentist random-effects network meta-analysis and estimated odds ratios with 95% CIs. Treatments were ranked using P-scores. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluation adapted for network meta-analysis.

Seven randomized controlled trials comprising 2126 patients (median age ≈69 years; ≈40% women; predominantly anterior circulation stroke) formed a coherent 6-node treatment network. For excellent functional recovery (modified Rankin Scale score, 0-1 at 90 days), IA alteplase 0.225 mg/kg showed higher odds versus control (odds ratio, 1.94 [95% CI, 1.31-2.87]), followed by tenecteplase 0.125 mg/kg (odds ratio, 1.90 [95% CI, 1.12-3.23]). Lower-dose tenecteplase regimens (0.0625 and 0.03125 mg/kg) and urokinase showed attenuated or uncertain effects. No regimen demonstrated a statistically significant difference in symptomatic intracranial hemorrhage or 90-day mortality compared with control, and safety estimates were imprecise. Global heterogeneity and inconsistency were low across outcomes.

In this dose-specific network meta-analysis of randomized controlled trials, IA alteplase 0.225 mg/kg and tenecteplase 0.125 mg/kg showed a signal consistent with improved excellent functional recovery after successful EVT for large-vessel occlusion acute ischemic stroke. Effects on broader functional outcomes were attenuated, and safety estimates were imprecise. These findings are hypothesis-generating and should inform the design of future dose-specific randomized controlled trials rather than guide current clinical practice.