Safety Outcomes of Tenecteplase Compared With Alteplase in Acute Ischemic Stroke: A Multicenter Retrospective Real-World Study

Acute ischemic stroke (AIS) affects over 795,000 individuals annually in the U.S. and remains a leading cause of death. Alteplase has long been the standard thrombolytic therapy for AIS, though tenecteplase has recently gained attention due to its favorable pharmacokinetics and simplified administration. Despite its increasing clinical use and recent FDA approval for AIS, safety data, particularly regarding bleeding outcomes, remain limited. The objective was to compare the incidence of symptomatic intracranial hemorrhage (sICH), major bleeding events, and in-hospital mortality between alteplase and tenecteplase in AIS. This retrospective, real-world, multi-center chart review compared 832 patients with AIS treated with alteplase or tenecteplase. The primary outcome was the incidence of sICH. Secondary outcome measures assessed were major bleeding and all-cause in-hospital mortality. There were no statistically significant differences in sICH (alteplase 8.8% vs tenecteplase 7.3%, <i>P</i> = 0.5), major bleeding (alteplase 10.9% vs tenecteplase 10.5%, <i>P</i> = 0.9), or in-hospital mortality (alteplase 5.1% vs tenecteplase 5.5%, <i>P</i> = 0.9). Higher NIHSS scores and mechanical thrombectomy were associated with increased risk of bleeding and mortality, regardless of the thrombolytic agent administered. Tenecteplase demonstrated a comparable safety profile to alteplase in the treatment of AIS, with no significant differences in sICH, major bleeding, or in-hospital mortality. Stroke severity and mechanical thrombectomy were stronger predictors of selected adverse outcomes than the choice of thrombolytic agent. These findings support tenecteplase as an alternative to alteplase for AIS thrombolysis.