Abstract Background and aims Endovascular thrombectomy has transformed acute ischemic stroke management, integrating intravenous thrombolysis into treatment pathways with routine access to endovascular therapy. The comparative effectiveness and safety of tenecteplase versus alteplase in these contemporary settings remain uncertain. We aimed to assess their real-world performance in populations representative of modern stroke care. Methods We conducted a focused synthesis of real-world comparative studies evaluating tenecteplase and alteplase. Eligible studies were observational cohorts or registries conducted in settings with routine access to endovascular thrombectomy, including large-vessel occlusion populations or systems where intravenous thrombolysis is standard care. Studies reporting functional outcomes, symptomatic intracranial hemorrhage, and/or mortality were included, prioritizing analyses adjusted using multivariable models or propensity-based methods. Results Twenty-nine real-world studies were included, comprising over 210,000 patients treated with intravenous thrombolysis. Evidence came from large national and international registries and from cohorts embedded in endovascular-capable stroke systems, including more than 5,000 patients from populations with 100% thrombectomy intent. Across these settings, functional outcomes with tenecteplase were largely comparable to those with alteplase, with some cohorts reporting favorable signals for tenecteplase in selected large-vessel occlusion or thrombectomy-focused populations. Rates of symptomatic intracranial hemorrhage were similar between treatments, with no consistent safety signal against tenecteplase. Mortality was mostly neutral, although several thrombectomy-focused cohorts reported numerically lower mortality with tenecteplase. Conclusions In real-world stroke populations treated within contemporary endovascular-capable systems, tenecteplase shows a benefit–risk profile comparable to alteplase. These findings support tenecteplase as a reliable thrombolytic option in modern stroke care and provide large-scale real-world evidence complementing randomized trial data. Conflict of interest Rocío Mesa Martínez: nothing to disclose, Javier Tejada García: nothing to disclose, Luis Augusto García Tuñón Villaluenga: nothing to disclose, Iria Beltrán Rodríguez: nothing to disclose, Patricia González Feito: nothing to disclose
Martínez et al. (Fri,) studied this question.