Bridging thrombolysis versus direct thrombectomy in acute ischemic stroke with large vessel occlusion: a network meta-analysis

BACKGROUND: Endovascular treatment (EVT) is the standard of care for acute ischemic stroke caused by large-vessel occlusion (AIS-LVO). The benefit of intravenous thrombolysis (IVT) before EVT remains uncertain, particularly for patients presenting directly to EVT-capable centers. Tenecteplase, with simpler administration and potential to improve early reperfusion, may offer an alternative to alteplase. This network meta-analysis evaluates the efficacy and safety of bridging therapy with different doses of alteplase or tenecteplase compared with direct EVT within 4.5 h of stroke onset. METHODS: A systematic literature search was conducted across the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases from their inception through September 20, 2025, to identify eligible randomized controlled trials (RCTs). Studies investigating EVT alone or EVT preceded by IVT with either alteplase or tenecteplase were included. The network meta-analysis was performed within a Bayesian framework, utilizing a fixed-effects model for the primary analysis. RESULTS: Nine RCTs comprising 3386 patients were included in the network meta-analysis. Regarding efficacy outcomes, 0.25 mg/kg tenecteplase + EVT demonstrated superior functional outcomes to EVT alone and 0.9 mg/kg alteplase + EVT, evidenced by significantly higher rates of functional independence (mRS 0-2) (OR 1.52, 95% CrI 1.14-2.04 vs. EVT alone; OR 1.42, 95% CrI 1.03-1.94 vs. alteplase + EVT) and freedom from disability (mRS 0-1) (OR 1.38, 95% CrI 1.02-1.89 vs. EVT alone; OR 1.43, 95% CrI 1.02-2.01 vs. alteplase + EVT). Based on the surface under the cumulative ranking curve (SUCRA), 0.4 mg/kg tenecteplase + EVT ranked highest for functional independence (mRS 0-2) with a SUCRA value of 0.855, while 0.25 mg/kg tenecteplase + EVT ranked second (SUCRA = 0.811). For successful reperfusion, 0.9 mg/kg alteplase + EVT demonstrated superiority over EVT alone (OR 1.28, 95% CrI 1.01-1.63). In terms of safety outcomes, 0.4 mg/kg tenecteplase + EVT was associated with a significantly increased risk of symptomatic intracranial hemorrhage compared with EVT alone (OR 5.29, 95% CrI 1.03-44.56), while 0.6 mg/kg alteplase + EVT showed a higher risk of any intracranial hemorrhage versus EVT alone (OR 2.02, 95% CrI 1.15-3.57). No statistically significant differences in death within 90 days were observed among any treatment strategies. CONCLUSIONS: In comprehensive consideration of efficacy and safety, 0.25 mg/kg tenecteplase + EVT may represent a preferable treatment option for AIS-LVO patients compared to other reperfusion strategies.