Implementation of tenecteplase for acute ischemic stroke: workflow and safety in routine care including off-label use

Introduction Tenecteplase is increasingly adopted as an alternative to alteplase for intravenous thrombolysis in acute ischemic stroke. However, real-world data describing complete institutional transitions, particularly in extended treatment windows and off-label clinical scenarios, remain limited. Methods We conducted a retrospective cohort study of consecutive patients treated with intravenous thrombolysis during the 12 months before and after a complete institutional transition from alteplase to tenecteplase (June 2023–May 2025). Primary endpoints were in-hospital workflow metrics (door-to-needle, door-to-imaging, imaging-to-needle, door-to-groin, and door-to-recanalization times). Safety outcomes included any intracranial hemorrhage and symptomatic intracranial hemorrhage according to the SITS-MOST definition. Outcomes were analyzed in the overall cohort, in patients treated beyond 4.5 h after symptom onset, and in patients receiving oral anticoagulation. Multivariable-adjusted and propensity score–based analyses, including augmented inverse probability of treatment weighting, were applied to account for baseline differences. Results Among 591 thrombolyzed patients (rt-PA n = 278; TNK n = 313), 31% were treated beyond 4.5 h and 14% under oral anticoagulation. Tenecteplase was associated with significantly shorter door-to-needle times (31 vs. 35 min; p = 0.004), primarily driven by reduced imaging-to-needle intervals (13 vs. 16 min; p = 0.004). Door-to-groin times were numerically shorter with tenecteplase but did not differ significantly (70 vs. 76 min; p = 0.07). Rates of any intracranial hemorrhage (8% vs. 7%; p = 0.61) and symptomatic intracranial hemorrhage (3% vs. 1%; p = 0.34) were comparable. Similar safety findings were observed in patients treated beyond 4.5 h after symptom onset and in those receiving oral anticoagulation, with consistent results across multivariable-adjusted and propensity score–based analyses. Conclusion Institutional transition to tenecteplase was associated with improved in-hospital workflow without evidence of increased hemorrhagic complications. These findings support the feasibility of implementing tenecteplase as the standard thrombolytic agent in routine comprehensive stroke center practice, including in extended treatment windows and selected off-label clinical scenarios.