Amesh A. Adalja, MD, FACP, FACEP, April 17, 2015
Sepsis is the final common pathway to severe morbidity and mortality for most infectious diseases. The immune cascade that underlies sepsis has both pro-inflammatory and immunosuppressive phases, which underlies the efforts to study the effects of immunomodulation on its clinical course. Of the myriad immunomodulators available, “statins” (HMG-CoA reductase inhibitors) have received much attention, and they have been advocated for the treatment of infectious diseases such as influenza and Ebola. These ubiquitous and widely prescribed cholesterol-lowering medications have broad effects. Observational studies have suggested a possible beneficial effect on mortality in sepsis, but such studies are often compromised by an inherent tendency to healthy user bias.
To untangle that bias, several randomized control trials have been conducted but they have failed to show benefit. However, pooled data from these randomized trials in a meta-analysis is an important way to determine whether a true benefit exists. Deshpande and colleagues from the Cleveland Clinic and Case Western University recently published such a meta-analysis in the American Journal of Medicine.
Deshpande and colleagues systematically surveyed the literature to find randomized controlled trials of statins whose endpoints included mortality in patients with sepsis; 7 trials that included 1,720 subjects met their inclusion criteria. All trials were placebo controlled and used consensus definitions for sepsis. Atorvastatin, simvastatin, and rosuvastatin were the statins employed.
In-hospital mortality was not found to differ between treatment and placebo groups, including in trials in which mortality was above 20% or below 20%. Similarly, no effect was found on 28-day hospital mortality. Type of statin and dose also did not influence the results.
The results of this study provide further evidence that, although statins are undoubtedly important medications with pleiotropic effects, their role in sepsis is clearly limited. As Deshpande et al write, “Further randomized controlled trials on the topic would seem to offer little value.” Nonetheless, immunomodulation in sepsis remains an important avenue of research, and other compounds might prove more fruitful.
Deshpande A, Pasupuleti V, Rothberg MB. Statin therapy and mortality from sepsis: a meta-analysis of randomized trials. Am J Med 2015;128:410-417.