Statins role in the prevention and treatment of sepsis

Pharmacol Res. 2014 Oct;88:31-40. doi: 10.1016/j.phrs.2014.04.010. Epub 2014 May 2.

Abstract

Sepsis is a complex disease with typically poor outcomes. While the onset of sepsis is typically infectious, the detrimental consequences follow pathogen toxin release that produces activation of numerous cytokines and a pro-inflammatory response. These same cytokines also stimulate activation of coagulation and inhibit natural fibrinolysis. Despite decades of research targeted against these pathways the development of sepsis and mortality in patients with sepsis remains high. While statins were developed for reducing cholesterol in patients with atherosclerotic disease, we now know they have a number of other properties which may be helpful in the prevention and treatment of sepsis. Statins have demonstrated the ability to reduce a number of pro-inflammatory cytokines known to be detrimental in the development and progression of sepsis. Statins have also demonstrated the ability to limit the coagulation response and promote fibrinolysis in the setting of sepsis. Based on these encouraging pharmacologic properties of statins a number of trials have been conducted evaluating the impact of statins on the prevention and treatment of sepsis. Most of the trials to date have been retrospective cohort trials, with very few prospective randomized trials. While some trials fail to demonstrate a benefit of statins, most trials suggest a reduction in the development of sepsis and/or other important sepsis related outcomes. While the laboratory and early clinical experience with statins are encouraging, randomized controlled trials will be need to fully define the role of statins in the prevention and treatment of sepsis.

Trial registration: ClinicalTrials.gov NCT00450840 NCT00528580 NCT00676897.

Keywords: Critical care; Inflammation; Intensive care; Sepsis; Statins.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Sepsis / drug therapy*
  • Sepsis / immunology
  • Sepsis / prevention & control

Substances

  • Anti-Inflammatory Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors

Associated data

  • ClinicalTrials.gov/NCT00450840
  • ClinicalTrials.gov/NCT00528580
  • ClinicalTrials.gov/NCT00676897