The impact of statin use on sepsis mortality

Abstract

•Statin use is associated with improved sepsis-related mortality.•Statin use is not related with shorter stay in hospital nor ICU.•The effectiveness of statin use during sepsis may be attributed to its pleiotropic effects beyond lipid-lowering properties. BACKGROUNDStatins 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.METHODSData 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 RESULTS90-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.CONCLUSIONSStatin 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. 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. 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. 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. 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.

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