The Impact of Statin Use on Sepsis Mortality

Background: Statins exert pleiotropic anti-inflammatory and antioxidant effects in addition to their cholesterol-lowering properties. This study aimed to investigate whether statin use is associated with improved outcomes of sepsis. Methods: Data from sepsis patients were extracted from the Medical Information Mart for Intensive Care IV database. Statin users were matched with non-users using propensity-score matching, to balance confounding factors between the groups. Mendelian Randomization (MR) analyses were performed using information from the UK Biobank dataset to explore the potential causal link between low-density lipoprotein cholesterol (LDL-C) levels and LDL-C lowering effects via genetically inhibiting β-hydroxy β-methylglutaryl-coenzyme A reductase and the susceptibility to sepsis, and the sepsis-related 28-day mortality. Main results: The study comprised 31,983 septic patients. 90-day mortality rate was lower among the 10,323 statin users when compared to matched non-users [hazard ratio (HR): 0.612, 95% CI: 0.571 to 0.655]. In-hospital mortality was also lower for statin users compared to non-users (11.3% vs. 17.8%, p<0.0001, HR: 0.590, 95% CI: 0.548 to 0.634). ICU or in-hospital length of stay were similar between statin users and matched non-users. In Cox proportional hazard models and with stratification by medical history of hyperlipidemia or myocardial infarction, we identify almost all sub-populations in which statin therapy was associated with a better outcome. MR analyses further pointed toward pleiotropic effects beyond lipid-lowering effects of statins on sepsis-related outcomes. Conclusions: Statin use is associated with improved outcomes following sepsis-related ICU admission, most likely from its pleiotropic properties, characterized by lower 90-day and in-hospital mortality among statin users.