Impact of sex in stroke thrombolysis: a coarsened exact matching study

BACKGROUND: It is not established whether sex influences outcome and safety following intravenous thrombolysis (IVT) in acute stroke. As a significant imbalance exists between the baseline conditions of women and men, regression analysis alone may be subject to bias. Here we aimed to overcome this methodical shortcoming by balancing both groups using coarsened exact matching (CEM) before evaluating outcome. METHODS: From our local prospective stroke database we analyzed consecutive patients who suffered anterior circulation stroke and received IVT from 1998 to 04/2013 (n = 1391, 668 female, 723 male). Data were preprocessed by CEM, balancing for age, NIHSS, lesion side, hypertension, diabetes, atrial fibrillation, smoking, coronary heart disease, and previous stroke, which yielded a matched cohort of 502 women and 436 men (n = 938). Outcome was estimated by adjusted binomial logistic regression analysis incorporating matched weights. RESULTS: No effect of sex was seen to predict good outcome (OR 1.04, CI 0.76–1.43) or mortality (OR 1.13, CI 0.73–1.73). However, female sex was a strong independent predictor of symptomatic intracerebral hemorrhage (sICH – ECASS-II definition, OR 3.62, CI 1.77-7.41) and fatal ICH (OR 4.53, CI 1.61-12.7). CONCLUSION: In balanced groups, the two sexes showed comparable outcomes following IVT. A novel finding was the higher rate of sICH and fatal ICH in women. In this analysis we also demonstrate how CEM can reduce multivariate imbalance and thereby improve estimates, already in crude, but more importantly, in adjusted regression analysis. Further investigations of multicentre data with improved analytical approaches that yield balanced sex-groups are therefore warranted.