Effect of Pre-Antibiotic Use Before First Stroke Incidence on Recurrence and Mortality: A Longitudinal Study Using the Korean National Health Insurance Service Database

Purpose: Clinical studies on dysbiosis and stroke outcomes has been insufficient to establish clear evidence. This study aimed to investigate the effects of pre-antibiotic use before a stroke event on secondary outcomes using a longitudinal population-level database. Patients and Methods: This retrospective cohort study included adults aged 55 years or older diagnosed with acute ischemic stroke (AIS) and acute hemorrhagic stroke (AHS) between 2004 and 2007. Patients were followed-up until the end of 2019, and the target outcomes were secondary AIS, AHS, and all-cause mortality. Multivariable Cox regression analyses were applied, and we adjusted covariates such as age, sex, socioeconomic status, hypertension, diabetes, and dyslipidemia. Pre-antibiotic use was identified from 7 days to 1 year before the acute stroke event. Results: We included 159,181 patients with AIS (AIS group) and 49,077 patients with AHS (AHS group). Pre-antibiotic use significantly increased the risk of secondary AIS in the AIS group (adjusted hazard ratio aHR, 1.03; 95% confidence interval CI, 1.01– 1.05; p = 0.009) and secondary AHS in the AHS group (aHR, 1.08; 95% CI, 1.03– 1.12; p < 0.001). Furthermore, pre-antibiotic use in the AIS group was associated with a lower risk of mortality (aHR, 0.95; 95% CI, 0.94– 0.96; p < 0.001). Conclusion: Our population-based longitudinal study revealed that pre-antibiotic use was associated with a higher risk of secondary stroke and a lower risk of mortality in the AIS and AHS groups. Further studies are needed to understand the relationship between dysbiosis and stroke outcomes. Keywords: brain-gut axis, dysbiosis, mortality, stroke