Abstract
BACKGROUND: Heparin may mitigate secondary brain injury in subarachnoid hemorrhage (SAH), but its effect on survival in non-traumatic SAH (NSAH) remains uncertain. This study aimed to investigate the association between early prophylactic heparin use (within 72 h of admission) and mortality outcomes in patients with NSAH. METHODS: We performed a retrospective cohort study using the Medical Information Mart for Intensive Care (MIMIC) and the eICU Collaborative Research Database (eICU-CRD). Patients were stratified by early heparin use. Cox models, Kaplan-Meier (KM) curves, subgroup analyses, and comprehensive propensity score-based sensitivity analyses were applied to assess the robustness of the observed associations. The primary outcome was in-hospital mortality; 28-, 90-, 180-, and 365-day mortality were secondary outcomes. Findings were validated using the eICU-CRD cohort. RESULTS: In the MIMIC-IV cohort, early heparin use was associated with lower in-hospital mortality (HR 0.62, 95% CI 0.39-0.97, p = 0.037), which was confirmed in the eICU-CRD cohort (HR 0.47, 95% CI 0.22-1.00, p = 0.049). Consistent reductions were also observed for 28-day (HR 0.57, p = 0.009), 90-day (HR 0.62, p = 0.010), 180-day (HR 0.63, p = 0.009), and 365-day mortality (HR 0.61, p = 0.004) in the MIMIC-IV cohort. Subgroup analyses and KM curves further supported these findings. Propensity score-based sensitivity analyses further validated the robustness of these findings in both cohorts. CONCLUSION: Early prophylactic heparin was associated with lower risk-adjusted short- and long-term mortality in NSAH.