AUTHOR=Zhao Weili , Zhang Xi , Zhao Yang , Zhao Ruijie , Liu Yalin TITLE=Comparative effectiveness and safety of tenecteplase versus alteplase for intravenous thrombolysis in acute ischemic stroke: a retrospective study JOURNAL=Frontiers in Neurology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1691168 DOI=10.3389/fneur.2025.1691168 ISSN=1664-2295 ABSTRACT=BackgroundTenecteplase has been proposed as a practical alternative to alteplase for intravenous thrombolysis in acute ischemic stroke. Although randomised trials have demonstrated noninferiority, data from real-world comparative cohorts remain limited.AimThis study evaluated functional and safety outcomes of tenecteplase compared with alteplase in a single-center cohort.MethodsWe retrospectively analysed consecutive patients with acute ischemic stroke who underwent intravenous thrombolysis with either tenecteplase or alteplase between April 2023 and April 2025. The primary endpoint was excellent functional recovery at 90 days, defined as a modified Rankin Scale (mRS) score of 0–1. Secondary endpoints included functional independence (mRS 0–2), early neurological improvement, and symptomatic intracranial hemorrhage (sICH). Multivariable logistic regression was used with adjustments for age, baseline NIHSS, diabetes, and atrial fibrillation. Subgroup analyses were performed by age, baseline stroke severity, and history of prior stroke.ResultsA total of 226 patients were included, of whom 147 received alteplase and 79 received tenecteplase. Patients receiving alteplase were older (68 vs. 65) and more frequently had diabetes (49.0% vs. 34.2%) or atrial fibrillation (18.4% vs. 7.6%). At 90 days, good functional outcome (mRS 0–2) was achieved in 27.9% overall (31.6% tenecteplase vs. 26.0% alteplase) and excellent outcome (mRS 0–1) in 20.4% (22.2% vs. 19.3%). Early neurological improvement occurred in 35.8% (42.2% vs. 31.6%). Rates of sICH were low (6.1% vs. 2.5%) and not significantly different after adjustment (aOR 0.41, 95% CI 0.06–1.72). After multivariable adjustment, tenecteplase did not show a statistically significant association with excellent functional recovery (aOR 1.42, 95% CI 0.75–2.70; p = 0.280) or with functional independence (aOR 1.57, 0.88–2.83; p = 0.131). Tenecteplase was linked with functional independence in patients with severe stroke (aOR 4.12, 95% CI 1.10–17.95; p = 0.044).ConclusionTenecteplase demonstrated comparable safety and functional outcomes to alteplase, with signals of potential benefit in patients with more severe strokes. These findings reinforce trial evidence supporting tenecteplase as a practical and effective alternative to alteplase.