Adjunctive intra-arterial thrombolysis with endovascular thrombectomy for acute large-vessel occlusion stroke: a network meta-analysis of randomized trials
Abstract
While endovascular thrombectomy (EVT) is standard care for acute ischemic stroke due to large vessel occlusion (AIS-LVO), but nearly half of patients with successful reperfusion do not achieve functional independence. Adjunctive intra-arterial thrombolysis (IAT) aims to address residual distal thrombi and microcirculatory impairment; however, the efficacy and safety of IAT in comparison with other thrombolytics remain uncertain. We conducted a network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing EVT alone vs. EVT combined with IAT using alteplase (ALT), tenecteplase (TNK), or urokinase (UK) in AIS-LVO patients. Primary outcomes were excellent clinical outcome (mRS 0–1) and functional independence (mRS 0–2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and all-cause mortality. Eight RCTs involving 2,564 patients were included. For excellent clinical (mRS 0–1), EVT + IA-ALT ranked highest [surface under the cumulative ranking curve (SUCRA) 96.2%], followed by EVT + IA-TNK (59.8%). Both showed significant benefits over EVT alone [EVT + IA-TNK vs. EVT: RR 1.20, 95% CI 1.05–1.39. EVT + IA-ALT vs. EVT: RR 1.40, 95% CI 1.21–1.63 and EVT + IA-TNK (0.125 mg/kg) vs. EVT: RR 1.54, 95% CI 1.07–2.20. EVT + IA-ALT (0.225 mg/kg) vs. EVT: RR 1.40, 95% CI 1.21–1.63]. For functional independence (mRS 0–2), EVT + IA-ALT also ranked highest, but no combination strategy showed a statistically significant benefit over EVT alone in pairwise comparisons. Regarding safety, point estimates for sICH risk did not differ significantly between combination strategies and EVT alone. However, EVT + IA-TNK demonstrated a statistically significant advantage over EVT + IA-ALT in terms of lower all-cause mortality (RR 1.58, 95% CI 1.01–2.46). EVT + IA-ALT and EVT + IA-TNK may improve excellent clinical outcome without a statistically significant increase in sICH; however, clinically important bleeding risk cannot be excluded. In exploratory indirect comparisons, EVT + IA-TNK was associated with lower all-cause mortality than EVT + IA-ALT, although this finding is based on sparse evidence and should be interpreted with caution. PROSPERO CRD420261465567.