Trends in sex differences of functional outcome after intravenous thrombolysis in patients with acute ischemic stroke

Background: Intravenous thrombolysis (IVT) is an approved treatment for patients with acute ischemic stroke irrespective of sex. However, the current literature on sex differences in functional outcomes following IVT is inconsistent. So far, a number of studies-including a previous analysis based on data from the Austrian Stroke Unit Registry (ASUR)-detected significant sex-related differences in functional outcome, while others did not report any differences between women and men. In addition, currently there is a lack of data on how sex-related differences evolve over time. Aims: To assess time trends of sex-related differences in functional outcome of ischemic stroke in a large nationwide cohort and to investigate associations of patient characteristics with functional outcome post thrombolysis in women and men. These data will offer crucial insights into whether sex differences in functional outcome persist despite the large advances in acute stroke treatment. Methods: We analyzed retrospective data of consecutive patients with acute ischemic stroke treated with IVT in 39 stroke centers contributing to the ASUR between 2006 and 2021. We included patients over 18 years of age diagnosed with an acute ischemic stroke who received IVT and with available data on functional outcome at 3 months after treatment. The primary outcome parameter was favorable functional outcome (modified Rankin Scale (mRS) of 0-2) at 3 months. Multivariable logistic regression analysis was performed in the overall population and stratified by sex to assess associations of baseline characteristics with functional outcome. Results: Among 11,840 patients receiving IVT, 2489 of 5503 (45.4%) women achieved favorable functional outcome compared to 3787 of 6337 (59.8%) men. Overall, female sex was a statistically significant predictor of functional outcome after thrombolysis, but additional predictors of outcome differed between women and men. Female sex was independently associated with decreased chances of achieving functional independency (adjusted odds ratio (adjOR) = 0.87, 95% confidence interval (CI) = 0.79-0.96, p = 0.005) and we detected a statistically significant improvement in functional outcome over time only in men (year of treatment, adjOR (per year) = 1.04, 95% CI = 1.02-1.06, p < 0.001) but not in women (adjOR (per year) = 1.01, 95% CI = 0.99-1.03, p = 0.280). Hypertension, smoking, and longer or unknown onset-to-door times were statistically significant predictors of outcome only in male patients, whereas atrial fibrillation, prior myocardial infarction, and longer door-to-needle times were significantly associated with outcome only in women. Conclusions: Sex differences in functional outcome after IVT for acute ischemic stroke are persisting over the past years. Results of our analysis can increase awareness and a resulting focus on sex differences in predictors of outcome could be helpful in mitigating these differences in the future by supporting a more individualized patient care in clinical routine. Follow-up analyses are needed to assess this potential impact and its effect in the future. Data access statement: Data from the Austrian Stroke Unit Registry can only be accessed by the employed statistician (D.M.), access inquiries have to be addressed to the registry's academic review board.