Editors' ChoiceSepsis

Statins Beyond Heart Disease: A New Treatment for the Sepsis Syndrome?

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Science Translational Medicine  02 Jan 2013:
Vol. 5, Issue 166, pp. 166ec4
DOI: 10.1126/scitranslmed.3005532

Sepsis is one of the most challenging diseases to treat. Despite decades of research, we still lack specific pharmacological interventions to treat sepsis syndrome. Statins are drugs that inhibit the mevalonate cascade, part of the cholesterol biosynthesis pathway. They have revolutionized the care of patients with cardiovascular diseases because of their pleiotropic anti-inflammatory effects leading to improved endothelial function. Several large observational studies have suggested that statin use may protect against bacteremia and sepsis. However, these prior studies were only correlative and could not confirm causation.

Patel et al. conducted a randomized, double-blinded, placebo-controlled trial of 40 mg of atorvastatin given daily for up to 28 days in patients with sepsis. They hypothesized that this acute treatment would reduce patients' likelihood of progression to severe sepsis, which was defined as sepsis with at least one organ failure.

The authors discovered that the atorvastatin group had a significantly reduced risk of converting to severe sepsis when compared with that of the placebo group (4% versus 24%, P = 0.007 with a number needed to treat of only five patients). The secondary outcomes assessed in this study—such as mortality, length of hospital stay, and transfer to intensive care—did not differ between the two groups of patients. The authors also confirmed proper absorption and systemic effect of the drug by measuring a reduction in serum lipid levels with statin treatment. Although the authors did not investigate the mechanism of atorvastatin's benefit, they did show that the statin-treated group had a reduced urinary albumin-creatinine ratio, which is a surrogate for microvascular endothelial injury.

This is the first randomized clinical trial to show a beneficial impact of acutely administering a statin for the treatment of sepsis by reducing the progression from sepsis to severe sepsis in statin-naïve ward patients. The authors concluded that the acute administration of statins in this population may help prevent organ dysfunction or failure.

This finding is important because therapies for sepsis are currently limited to infection source control and antibiotics. Specific pharmacological interventions do not exist, and many have previously failed in clinical trials or during post-trial use in the community.

The mechanism of statin benefit in sepsis will require investigation in animal models and cell culture. By understanding how the statins work, additional novel inhibitors can be developed to treat sepsis, one of the most recalcitrant diseases known to man.

J. M. Patel et al., Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial). Crit. Care, published online 11 December 2012 (10.1186/cc11895). [Abstract]

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