Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med 2014 Jun 05;370(23):2191-200
Date
05/20/2014Pubmed ID
24835849Pubmed Central ID
PMC4241052DOI
10.1056/NEJMoa1401520Scopus ID
2-s2.0-84901759539 (requires institutional sign-in at Scopus site) 415 CitationsAbstract
BACKGROUND: In the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS.
METHODS: We conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure-free days to day 14.
RESULTS: The study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P=0.21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P=0.96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was associated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P=0.01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P=0.003). Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range.
CONCLUSIONS: Rosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction. (Funded by the National Heart, Lung, and Blood Institute and the Investigator-Sponsored Study Program of AstraZeneca; ClinicalTrials.gov number, NCT00979121.).
Author List
National Heart, Lung, and Blood Institute ARDS Clinical Trials Network, Truwit JD, Bernard GR, Steingrub J, Matthay MA, Liu KD, Albertson TE, Brower RG, Shanholtz C, Rock P, Douglas IS, deBoisblanc BP, Hough CL, Hite RD, Thompson BTMESH terms used to index this publication - Major topics in bold
AdultAged
Creatine Kinase
Double-Blind Method
Female
Fluorobenzenes
Hospital Mortality
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Liver Failure
Male
Middle Aged
Pyrimidines
Renal Insufficiency
Rosuvastatin Calcium
Sepsis
Sulfonamides
Survival Analysis
Treatment Failure