Statin Use and Mortality among Patients Hospitalized with Sepsis: A Retrospective Cohort Study within Southern California, 2008–2018

BACKGROUND: Despite early goal-directed therapy, sepsis mortality remains high. Statins exhibit pleiotropic effects. OBJECTIVE: We sought to compare mortality outcomes among statin users versus nonusers who were hospitalized with sepsis. METHODS: Retrospective cohort study of patients (age ≥18 years) during 1/1/2008–9/30/2018. Mortality was compared between statin users and nonusers and within statin users (hydrophilic versus lipophilic, fungal versus synthetic derivation, and individual statins head-to-head). Multivariable Cox regression models were used to estimate hazard ratios (HR) for 30-day and 90-day mortality. Inverse probability treatment weighting (IPTW) analysis was performed to account for indication bias. RESULTS: Among 128,161 sepsis patients, 34,088 (26.6%) were prescribed statin drugs prior to admission. Statin users compared to nonusers had a 30-day and 90-day mortality HR (95% CI) of 0.80 (0.77–0.83) and 0.79 (0.77–0.81), respectively. Synthetic derived statin users compared to fungal derived users had a 30- and 90-day mortality HR (95% CI) of 0.86 (0.81–0.91) and 0.85 (0.81–0.89), respectively. Hydrophilic statin users compared to lipophilic users had a 30-day and 90-day mortality HR (95% CI) of 0.90 (0.81–1.01) and 0.86 (0.78–0.94), respectively. Compared to simvastatin, 30-day mortality HRs (95% CI) were 0.85 (0.66–1.10), 0.87 (0.82–0.92), 0.87 (0.76–0.98), and 1.22 (1.10–1.36) for rosuvastatin, atorvastatin, pravastatin, and lovastatin, respectively. CONCLUSION: Statin use was associated with lower mortality in patients hospitalized with sepsis. Hydrophilic and synthetic statins were associated with better outcomes than lipophilic and fungal-based preparations.