Prior Statin Use Is Associated with Decreased Mortality and Lower Levels of Liver and Brain Organ Failure Scores in Sepsis - A Matched Observational Study

Abstract

Background: Statin use is associated with a decreased rate of severe sepsis. The objective of this paper is to quantify the level of organ dysfunction of patients with and without statin use prior to hospitalization. Methods: MIMIC-III was searched for adult sepsis patients. Immunosuppressed patients were excluded. Organ dysfunction was defined as alterations in Sequential Organ Failure Assessment (SOFA) score components or laboratory values. Other endpoints examined include 28-day, 90-day, and in-hospital mortality. All analyses were adjusted for Elixhauser comorbidity index components, age, gender, ethnicity, and year of admission and used doubly robust estimation. In a sensitivity analysis, the effect of statin potency on organ dysfunction was analyzed. Findings: 3,091 statin users and non-users were matched. In the matched cohort, mean age was 72 years, 54% of patients were female, and 31% had diabetes. The odds of mortality at day 28 (0.78), day 90 (0.75), and in the hospital (0.78) were significantly lower for those on statins (p=0.001; p<0.001; and p=0.003, respectively). Central nervous system (CNS, -14% change) and hepatic SOFA (-27% change) component scores were also significantly lower for statin users (p < 0.05). No significant difference was found for other measures of organ failure. Statin potency had statistically significant effects on day-28, day-90, and in-patient mortality, as well as coagulation, hepatic, and CNS components of the SOFA score. Interpretation: Statin use prior to sepsis was associated with dose-dependent lower short-term mortality that was clinically and statistically significant. This mortality benefit might be explained by neuro- and hepato-protective effects. Funding Statement: National Institutes of Health (NIBIB grant R01 EB017205). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The MIMIC III database is an open-access, publicly available dataset whose use has been approved by the institutional review boards of the BIDMC and Massachusetts Institute of Technology in Boston and Cambridge, Massachusetts, respectively (2001-P001699/3).