EXPLORING NOVEL EFFECTS OF STATINS ON SEPSIS MORTALITY WITHIN A REAL-WORLD SETTING

Abstract

SESSION TITLE: Diagnostic and Prognostic Insights into Sepsis SESSION TYPE: Original Investigations PRESENTED ON: October 18-21, 2020 PURPOSE: Statins have been suggested to attenuate the severity of sepsis. They have demonstrated antimicrobial properties both in vivo and in vitro. Fungal-derived statins may accomplish this due to their similarities to penicillin. Another mechanism may be related to statins’ lipophilic properties, disrupting lipid membranes resulting in cell death. The pleiotropy of effects including anti-inflammatory, immunomodulatory, and anti-cancer properties have been well characterized. We compared mortality outcomes in statin users versus non-users within a real world setting of Kaiser Permanente Southern California (KPSC). Additionally, mortality was compared among statin users based on fungal versus synthetic-derived and lipophilic versus hydrophilic statins. METHODS: A retrospective cohort study of patients admitted to hospitals within the KPSC health care system admitted for sepsis in the period 1/1/2008-9/30/2018. Sepsis was identified based on the International Classification of Diseases coding. Use of statin was defined as individuals who had filled at least two prescriptions for a statin. Short-term mortality in septic patients was analyzed among comparison groups: statin versus non-statin, hydrophilic versus lipophilic, and fungal versus synthetic derivation. For univariate analysis of categorical variables, we used Pearson chi-square test. For continuous variables, we used Wilcoxon rank-sum test. Multivariable Cox regression models were used to estimate hazard ratios (HR) 30 and 90-day mortality with adjustment for age, race, sex, and comorbidities determined as risk factors for sepsis. All statistical analyses were performed using SAS EG version 7.1 (SAS Institute, Cary, NC USA). P-value <0.05 was considered statistically significant. RESULTS: 137,019 patients were included, of which 36,908 were taking statins. With non-statin users as reference, differences in the 30-day and 90-day mortality HR’s (95% CI) for statin users were 0.79; (0.77-0.82) and 0.79; (0.77-0.81), respectively. Lipophilic compared to hydrophilic statin users had a 30-day and 90-day mortality HR of 1.13; (1.02-1.26) and 1.17; (1.07-1.28), respectively. Fungal derived statins compared to synthetic derived statin users had a 30-day and 90-day mortality HR of 1.12; (1.06-1.19) and 1.14; (1.09-1.20), respectively. CONCLUSIONS: In patients admitted with sepsis, we observed that statin users had lower mortality compared to non-statin users. Hydrophilic statins and synthetic statins had lower mortality outcomes than lipophilic and fungal derived statins, respectively. Our findings suggest a potential benefit of statins in patients with sepsis. Furthermore, based on their mechanism, certain statins may have a greater protective effect in the course of sepsis. CLINICAL IMPLICATIONS: For populations who are at greater risk for sepsis (immunocompromised, diabetics, elderly) and require a statin, use of certain statins may be a consideration. DISCLOSURES: No relevant relationships by Michael Gould, source=Web Response No relevant relationships by Brannen Liang, source=Web Response No relevant relationships by John Sim, source=Web Response No relevant relationships by Kenneth Wei, source=Web Response No relevant relationships by Su-Jau Yang, source=Web Response