The role of statin therapy in sepsis

OBJECTIVE: To systematically review the evidence evaluating the role of statin therapy in sepsis. DATA SOURCES: MEDLINE, EMBASE, and PubMed were searched (1980-January 2007) for English-language clinical trials that evaluated the use of statins and the development and treatment of sepsis in human subjects. Search terms included statin, HMG-CoA reductase inhibitor, bacteremia, sepsis, septic shock, septicemia, and severe sepsis. In addition, pertinent references from identified articles were obtained. STUDY SELECTION AND DATA EXTRACTION: Only clinical trials with primary efficacy outcomes of mortality, incidence of sepsis, and severe sepsis were included. DATA SYNTHESIS: Seven retrospective and 2 prospective cohort studies were included in this review. One was excluded because the patient population was not experiencing sepsis. Three studies demonstrated a reduced mortality with statin use while 2 other studies did not demonstrate this mortality benefit. One study suggested increased mortality with statin use in sepsis. Three studies showed a reduced incidence of development of sepsis or sepsis-related outcomes, while one study did not. The observational and retrospective nature of these studies and the higher rate of cardiovascular comorbidities in the statin groups may have allowed for a confounding influence. The conflicting results and heterogeneity between the studies makes the observed association between statin use and incidence of sepsis and sepsis-related mortality inconclusive. The clinical benefit of statin therapy in sepsis remains to be determined. CONCLUSIONS: There is an association between statin use and a lower incidence of sepsis and sepsis-related mortality. However, a causal relationship between statin use and reduced sepsis-related mortality has not yet been established. Currently, statins cannot be recommended for sepsis prevention or treatment until controlled trials are performed.