Comparative effectiveness of enoxaparin versus unfractionated heparin for 30- and 90-day mortality in sepsis patients without severe renal dysfunction: a retrospective cohort study

Background Although enoxaparin is known to be superior to UFH for thromboprophylaxis, the comparative effect of enoxaparin versus UFH on mortality in sepsis remains unknown. To address this gap, we compared the two agents in sepsis patients without severe renal impairment, thereby minimizing confounding due to differential drug clearance. Methods In this retrospective cohort study, we analyzed data from the eICU Collaborative Research Database. We included adult patients with sepsis and no severe renal impairment (eGFR ≥ 30 mL/min/1.73 m 2 ) who received prophylactic anticoagulation with either enoxaparin or UFH. The primary outcomes were 30-day ICU mortality and 90-day in-hospital mortality. Survival analyses were performed using Kaplan–Meier estimates and Cox proportional hazards models. Sensitivity analyses were conducted using inverse probability of treatment weighting. Results A total of 2,341 patients were enrolled (1,260 in the enoxaparin group and 1,081 in the UFH group). After adjusting for confounders, multivariate Cox regression showed that the hazard ratio (HR) for enoxaparin versus UFH was 0.94 (95% CI: 0.67–1.32, P = 0.726) for 30-day ICU mortality and 0.86 (95% CI: 0.66–1.12, P = 0.271) for 90-day in-hospital mortality. Subgroup analyses showed no significant heterogeneity across predefined strata of age, sex, or BMI (all P for interaction >0.05). These findings were supported by inverse probability of treatment weighting analysis. Conclusions In this cohort of sepsis patients without severe renal impairment, enoxaparin was associated with numerically lower but not statistically significant hazard ratios for both 30-day ICU and 90-day in-hospital mortality compared with UFH. These findings do not establish the superiority of either agent. Larger, prospective studies are warranted to confirm the observed associations.