Background: Unknown onset strokes (UOS) represent up to 20% of all AIS. For these patients, alteplase (tPA) has been shown to be safe and likely effective when screened by CTP or MRI based protocols. There is limited data on Tenecteplase (TNK) safety and efficacy for this population. We compared patients who received tPA versus TNK with UOS. Methods: Data were retrospectively abstracted from 2019-2025 for patients who received thrombolytics for UOS within a large 15 hospital integrated regional healthcare system in Southern California. For UOS, tPA was primarily used until 2024. After 2024, TNK was primarily used. The baseline characteristics including age, race, and vascular risk profile were auto abstracted, whereas safety and efficacy data was manually abstracted. Data was analyzed using chi squared, t-tests and Wilcoxan Rank Sum tests. Results: Seventy-six patients received UOS thrombolytics. Fifty-nine patients received tPA and seventeen patients received TNK. Nineteen patients were selected by CTP perfusion and fifty-seven were selected by MRI. Baseline characteristics were well matched. Between tPA and TNK, we found no significant difference in 90-day mortality (3 5%) tPA vs 1 {7% TNK. OR 1. 73 p=0. 6), 90 day mRS 0-2 (33 60% tPA vs 5 36% TNK. OR 0. 39. p=0. 13) or symptomatic intracerebral hemorrhage (1 1. 7% tPA vs 1 6% TNK. OR 4. 19 p=0. 24). There was no difference in door to needle times for TNK (96 mins tPA vs 83 mins TNK p=0. 17). CTP based treatment had faster door to needle times than MRI based treatment (87 mins CTP vs 95 mins MRI p=0. 014). While MRI had a comparable rate of symptomatic intracerebral hemorrhage (1 5% CTP vs 1 1. 7% MRI. OR 0. 26 p=0. 27), it had a lower rate of asymptomatic intracerebral hemorrhage (4 21% CTP vs 1 1. 7% MRI. OR 0. 09 p=0. 02). Conclusion: In this retrospective comparative analysis of patients who received TNK versus tPA with UOS, we found no major differences in safety or efficacy between the tPA and TNK. Patients treated via an MRI based protocol had longer door to needle times but had lower asymptomatic hemorrhage rates. TNK is likely as safe as tPA for patients with UOS and may be considered an alternative for tPA screened by MRI or CTP.
Nguyen et al. (Thu,) studied this question.