Thrombolysis-to-Puncture Time Determines the Differential Effect of Tenecteplase Versus Alteplase in Large Vessel Occlusion

BACKGROUND: Tenecteplase improves reperfusion and functional outcomes compared with alteplase in patients with large vessel occlusion. We assessed whether this superiority varies with thrombolysis-to-puncture time (TTP). METHODS: This retrospective analysis of a prospective multicenter cohort included patients with large vessel occlusion who received bridging therapy with either tenecteplase or alteplase between January 2022 and September 2025. Patients were stratified by TTP (<60 versus ≥60 minutes). We subsequently assessed the association of TTP with efficacy and safety outcomes between the alteplase and tenecteplase groups using multivariable logistic regression adjusted for age, baseline National Institutes of Health Stroke Scale score, and time from stroke onset to arterial puncture. Functional independence was defined as a modified Rankin Scale score of 0 to 2 at 3 months. RESULTS: =0.111). No between-agent differences were significant with TTP ≥60 minutes. Safety outcomes were comparable, but each 30-minute TTP increase independently elevated hemorrhagic risks for both agents. CONCLUSIONS: The recanalization superiority of tenecteplase over alteplase is time-dependent, evident only within a TTP <60 minutes. Although the translation of this advantage into functional outcome was not statistically modified by time, optimizing workflow to achieve this rapid window maximizes the potential benefit of tenecteplase, which should be prioritized in capable settings.