Effect of Alteplase on Ischemic Stroke Mortality Is Dependent on Stroke Severity

Objective Although intravenous alteplase (IV‐tPA) has a beneficial effect on functional outcome after ischemic stroke (IS), prior studies of IV‐tPA's impact on post‐stroke mortality did not have sufficient representation of more severe stroke. Methods We determined if the interaction between the baseline National Institutes of Health (NIH) Stroke Scale (NIHSS) and IV‐tPA modified the risk of mortality after IS in two cohorts: (1) National Inpatient Sample 2016–2020, and (2) a harmonized cohort of IS patients from the NINDS IV‐tPA, ALIAS part 2, SHINE, FAST‐MAG, IMS‐III, POINT, and DEFUSE 3 trials. We fit logistic regression models to the outcome of in‐hospital mortality (National Inpatient Sample [NIS] cohort) or mortality within 90 days (harmonized cohort), adjusted for baseline variables. Results We included 198,668 patients in the NIS cohort, of which 14.0% received IV‐tPA and 3.4% died in hospital. We included 7,138 patients in the harmonized cohort, of which 33.2% received IV‐tPA and 9.4% died by 90 days. Mortality in the NIS cohort was associated with older age, female sex, non‐Hispanic white race, atrial fibrillation, and higher NIHSS. In the harmonized cohort, mortality was associated with older age, diabetes, atrial fibrillation, and higher NIHSS. In both cohorts, the interaction between NIHSS and IV‐tPA was significant. In the NIS cohort, the separation became significant at NIHSS 15 and in the harmonized cohort at NIHSS 23, at which point, IV‐tPA began to have a significant benefit for both in‐hospital and 90‐day mortality, respectively. Interpretation IV‐tPA is associated with a reduction in both in‐hospital and 90‐day mortality for patients with more severe IS. ANN NEUROL 2023;93:1106–1116