Intra-arterial thrombolysis agents following endovascular thrombectomy for acute ischemic stroke: a network...

Endovascular thrombectomy (EVT) is the standard treatment for acute ischemic stroke caused by large-vessel occlusion (AIS-LVO), but incomplete microvascular reperfusion often limits recovery. The 2026 American Heart Association/American Stroke Association guideline suggests that adjunctive intra-arterial thrombolysis (IAT) may be considered after successful EVT to target residual microthrombi, yet the comparative efficacy and safety of different IAT strategies remain unclear. This study therefore compared the efficacy and safety of various IAT strategies following successful EVT in AIS-LVO.

We systematically searched MEDLINE, Embase, and Cochrane CENTRAL from their inception through 26 February 2026, for randomized controlled trials (RCTs) comparing EVT alone or with IAT. A Bayesian network meta-analysis using a fixed-effects model was conducted.

Seven RCTs including 2,131 patients were analyzed. Compared with EVT alone, EVT + 0.225 mg/kg alteplase (ALT) or 0.125 mg/kg tenecteplase (TNK) significantly improved excellent functional outcome (modified Rankin Scale [mRS] 0-1) (OR 1.95, 95% CrI 1.32-2.89; OR 1.91, 95% CrI 1.12-3.27), while EVT + 0.0625 mg/kg TNK was associated with a significantly higher risk of any intracranial hemorrhage (aICH) (OR 1.53, 95% CrI 1.13-2.07). No statistically significant differences were observed for functional independence (mRS 0-2), favorable outcome (mRS 0-3), symptomatic intracranial hemorrhage (sICH), or 90 day mortality. Surface under the cumulative ranking curve (SUCRA) analysis indicated that EVT + 0.225 mg/kg ALT ranked highest for functional independence (mRS 0-2), but also ranked higher for the risk of 90 day mortality. In contrast, EVT + 0.0625 mg/kg TNK ranked highest for favorable outcome (mRS 0-3), while also ranking highest for the risk of sICH and aICH.

Not all IAT strategies showed statistically significant efficacy, but EVT + 0.225 mg/kg ALT or 0.125 mg/kg TNK significantly improved excellent functional outcomes. SUCRAs suggested that EVT + 0.225 mg/kg ALT may provide broader functional benefits with a lower risk of sICH. Further confirmation in head-to-head RCTs is warranted.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251250195, identifier CRD420251250195.