Heparin therapy improved outcomes in elderly critically ill patients with sepsis: A marginal structural model analysis from the MIMIC-IV database

Abstract Background Heparin, a multitarget agent that protects against sepsis, has been extensively studied. The efficacy of heparin therapy to provide a survival advantage for elderly, critically ill patients with sepsis remains inconclusive. The aim of this study was to investigate the efficacy of heparin therapy in elderly, critically ill patients with sepsis. Methods We identified elderly septic patients (aged ≥ 65 years) from the Medical Information Mart for Intensive Care (MIMIC-IV) database. We employed propensity score matching (PSM), marginal structural Cox models (MSCMs), and E-value analyses to account for confounding factors. Heparin was administered within 48 h of ICU admission. The primary endpoint was ICU mortality, while secondary outcomes included 28-day, 90-day, and in-hospital mortality, along with haemorrhage occurrence. Results A total of 3866 elderly patients with sepsis were enrolled in the study, with 1434 patients receiving heparin and 2432 patients without heparin therapy. Early heparin therapy significantly reduced ICU mortality (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.48–0.81) and haemorrhage occurrence (HR 0.43, 95% CI 0.33–0.56) across the overall population with PSM. However, early heparin therapy did not significantly improve 28-day, 90-day, or in-hospital mortality. MSCMs further confirmed that heparin administration reduced ICU mortality (HR 0.58, 95% CI: 0.44–0.75) in the general population. Stratification analysis using MSCMs indicated that heparin administration was associated with a reduced ICU mortality rate among patients on ventilation (HR 0.55, 95% CI 0.41–0.74) and with AKI (HR 0.59, 95% CI 0.45–0.78) (P < 0.001). Conclusions Heparin administration to elderly patients at the early stages of sepsis is effective in reducing ICU mortality without increasing the risk of bleeding. Prospective studies are needed to verify this findings.