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. Patients with a history of receiving prescriptions for statins (i.e. atorvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin) 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: 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). Statin use was associated with better outcome in all investigated subpopulations apart from patients with severe liver disease. 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.
Keywords: Mendelian randomization; Pharmacoepidemiology; Prognosis; Propensity score matching; Sepsis-3; Statins.
Copyright © 2024. Published by Elsevier Inc.