Abstract Background and aims Tenecteplase is increasingly used as an alternative to alteplase for intravenous thrombolysis in acute ischemic stroke, yet uncertainty remains regarding its real-world effectiveness. We aimed to synthesize real-world evidence comparing tenecteplase and alteplase, focusing on functional outcomes, symptomatic intracranial hemorrhage (sICH), and mortality. Methods We conducted a structured comparative synthesis of real-world studies evaluating tenecteplase versus alteplase in acute ischemic stroke. Eligible studies included large national and multinational stroke registries, propensity score–matched observational cohorts, and secondary or post-hoc analyses derived from randomized controlled trials. Functional outcomes were assessed using modified Rankin Scale (mRS)–based endpoints, including shift analyses. Safety outcomes included sICH as defined by individual studies and mortality. Adjusted effect estimates were extracted as reported. Results Twelve studies comprising more than 100,000 patients were included. Across large real-world registries, tenecteplase showed functional outcomes comparable to alteplase, with no significant differences in favorable mRS outcomes. Several adjusted analyses demonstrated a shift toward improved functional outcomes with tenecteplase in selected populations. Rates of sICH were consistently similar or lower with tenecteplase, including a significant reduction in one large multicenter registry. No study reported increased mortality with tenecteplase, and several analyses showed lower mortality compared with alteplase. One national registry reported worse outcomes for a composite safety endpoint, a finding not replicated elsewhere. Conclusions Across real-world evidence, tenecteplase demonstrates effectiveness comparable to alteplase for acute ischemic stroke, with a favorable safety profile and no signal of increased mortality. These findings support tenecteplase as a safe and robust alternative to alteplase in routine clinical practice. 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.