Sex differences in survival, functional outcomes and health-related quality of life are mostly due to women's greater age, more severe stroke and pre-stroke health compared to men: The INternational STRoke oUtComes sTudy (INSTRUCT).

Background: The sex differences in stroke outcome may be due to confounding. We established an individual participant data meta-analysis to establish the causes of sex differences in outcome after stroke. Method(s): We obtained data on strokes (1987-2013) from 13 population-based studies including socio-demographics, stroke-related factors, pre-stroke health and 1-year outcomes (mortality, functional outcome, health-related quality of life [HRQoL]). For women compared to men, we estimated the relative risk of mortality and poor functional outcome using log binomial regression and the mean differences in HRQoL using linear regression. Study-specific adjusted models were combined using random effects meta-analysis. Result(s): There were 16,957 participants followed up at 1 year. Women were 35% more likely to be deceased (RR 1.35 95% CI 1.24-1.47) and 32% more likely to have a poor functional outcome (RR 1.32 95% CI 1.18-1.48) than men.Women had lower mean HRQoL than men: EQ5D -0.064 (95% CI -0.094, -0.035) and AQoL -0.135 (95% CI -0.196, -0.074). For mortality, these differences were explained by age, stroke severity and atrial fibrillation; whereas for functional outcomes the differences were mostly attenuated by age, stroke severity and pre-stroke function. The sex differences in HRQoL remained after accounting for a range of confounders including age, severity, pre-stroke function and vascular risk factors. Conclusion(s): The worse outcome after stroke in women compared to men is mostly due to their advanced age and more severe strokes. Ensuring equal access to acute care and primary and secondary prevention, particularly for the elderly, should make outcomes more equitable.