Statin use and all-cause mortality in critically ill ischemic stroke patients: a time-dependent Cox analysis with external validation highlighting enhanced survival benefits in dementia subgroups

Introduction Ischemic stroke is a leading cause of mortality and disability, but the effect of statins on survival in critically ill patients, especially those with dementia, remains unclear. Methods This retrospective cohort study analyzed 1,964 patients from MIMIC-IV and validated findings in 4,255 external cases. Time-dependent Cox, IPTW, and PSM were applied. Results Statin use was significantly associated with reduced mortality at 30, 90, 180 days, and 1 year, though the effect attenuated over time. A significant statin-dementia interaction was observed, with greater benefit in dementia patients (adjusted HR = 0.548; NNT = 7 vs. 13). The strongest protection occurred immediately post-admission (74.1% risk reduction) and waned by 1 year. Results were robust in sensitivity and external validation. Discussion In conclusion, statin therapy improves short-to-medium-term survival in critically ill ischemic stroke patients, with potential additional benefits observed in those with dementia. These findings support early statin use and suggest dementia as a potential effect modifier, though prospective validation with standardized cognitive assessments is needed.