Sex Differences and Functional Outcome After Intravenous Thrombolysis

There is a growing recognition of importance of sex in stroke outcome. More women are affected by stroke because of their longer life expectancy and have a worse functional outcome and a lower quality of life after stroke compared with men. In patients with acute stroke, previous research has also shown sex to affect outcome after intravenous thrombolysis (IVT) treatment; although outcome was similar between men and women treated with placebo, outcome was better in women after IVT. The biological explanation for this difference remains unclear. A possible explanation could be the difference in recanalization. Women have more cardioembolic strokes, with uniform fibrin-rich clots and therefore a higher affinity of alteplase, resulting in more frequent, faster, and complete recanalization. Another suggested mechanism could be a difference in endogenous fibrinolysis because of differences in sex hormones between men and women. Estrogen has an indirect influence on the controlling of the fibrinolytic system, as well as a direct neuroprotective activity. However, there are no convincing data to support these hypotheses. Background and Purpose—Women have a worse outcome after stroke compared with men, although in intravenous thrombolysis (IVT)–treated patients, women seem to benefit more. Besides sex differences, age has also a possible effect on functional outcome. The interaction of sex on the functional outcome in IVT-treated patients in relation to age remains complex. The purpose of this study was to compare outcome after IVT between women and men with regard to age in a large multicenter European cohort reflecting daily clinical practice of acute stroke care. Methods—Data were obtained from IVT registries of 12 European tertiary hospitals. The primary outcome was poor functional outcome, defined as a modified Rankin scale score of 3 to 6 at 3 months. We stratified outcome by age in decades. Safety measures were symptomatic intracranial hemorrhage and mortality at 3 months. Results—In this cohort, 9495 patients were treated with IVT, and 4170 (43.9%) were women with a mean age of 71.9 years. After adjustments for baseline differences, female sex remained associated with poor functional outcome (odds ratio, 1.15; 95% confidence interval, 1.02–1.31). There was no association between sex and functional outcome when data were stratified by age. Symptomatic intracranial hemorrhage rate was similar in both sexes (adjusted odds ratio, 0.93; 95% confidence interval, 0.73–1.19), whereas mortality was lower among women (adjusted odds ratio, 0.83; 95% confidence interval, 0.70–0.99). Conclusions—In this large cohort of IVT-treated patients, women more often had poor functional outcome compared with men. This difference was not dependent on age. (Stroke. 2017;48:699-703. DOI: 10.1161/STROKEAHA.116.014739.)