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.