Tenecteplase or alteplase for acute ischemic stroke beyond 4.5 hours of last known well. A pooled analysis of the TETRIS and EVATRISP registries.

Background-Intravenous thrombolysis with tenecteplase within 4.5hrs after ischemic stroke is non-inferior to alteplase. However, it is uncertain whether this is also true in patients last known to be well more than 4.5hrs before treatment initiation (LKW >4.5hrs). We aimed to compare tenecteplase and alteplase in this population using data from two large multicenter registries.Methods-Pooled retrospective analysis of acute stroke patients LKW >4.5hrs treated with tenecteplase 0.25 mg/kg (TETRIS registry) or alteplase 0.9 mg/kg (EVATRISP registry plus 4 French centers participating in TETRIS) based on the results of MRI or perfusion CT. Excellent functional outcome at 3 months (mRS 0-1) was the primary outcome. Secondary outcomes were mRS 0-2, shift analysis of the mRS, any intracranial hemorrhage (ICH), symptomatic ICH, and death. Propensity score overlap weighting (PSOW) was used to account for imbalance in baseline characteristics.Results-897 patients (tenecteplase: n=419; alteplase: n=478) were included between 2015 and 2024 (mean age: 74 [IQR:64-84]; median NIHSS 11 [6-17]; unknown stroke onset in 777 [86.6%] patients). At 3 months, mRS 0-1 was achieved in 138 (32.9%) and 178 (37.2%) patients treated with tenecteplase and alteplase, respectively (crude OR 0.83 [95%CI 0.63-1.09]; PSOW-OR 0.92 [95%CI 0.66-1.30]). Compared with alteplase, tenecteplase was not significantly associated with mRS 0-2 (PSOW-OR 0.78 [95%CI 0.56-1.08]) or better functional outcome over the whole range of the mRS (PSOW-common OR 0.83 [95%CI 0.62-1.11]). Tenecteplase was associated with significantly higher odds of any ICH (PSOW-OR: 1.79 [95%CI 1.25-2.57]), but not sICH (PSOW-OR 1.12 [95%CI 0.61-2.05]).Conclusions-The functional outcomes of patients LKW >4.5hrs treated with tenecteplase or alteplase did not significantly differ in this pooled analysis of two observational registries. However, the direction of the associations did not favor tenecteplase over alteplase and therefore more comparative studies -ideally randomized- are needed before routinely switching to tenecteplase in this population.