In a recent study, patients with acute respiratory distress syndrome who were not receiving statins were assigned to receive simvastatin or placebo. At 28 days, there were no significant between-group differences in survival or in the number of ventilator-free days.
The acute respiratory distress syndrome (ARDS) is a common, devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and by multiple organ failure. In ARDS there is an uncontrolled inflammatory response that results in alveolar damage, with the exudation of protein-rich pulmonary-edema fluid in the alveolar space that results in respiratory failure.
• What is the basis of interest in statins as a possible treatment for ARDS?
The inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase with statins has been shown to modify a number of the underlying mechanisms implicated in the development of ARDS. Statins decrease inflammation and histologic evidence of lung injury in murine models of ARDS. Simvastatin reduced pulmonary and systemic inflammatory responses in a human model of ARDS induced by lipopolysaccharide inhalation. In addition, in a small, single-center, randomized, placebo-controlled study, simvastatin ameliorated nonpulmonary organ dysfunction and was safe.
•What were the outcomes of this study, which compared simvastatin to placebo for the treatment of ARDS?
The primary outcome, the number of ventilator-free days, did not differ significantly between the two study groups (12.6+/-9.9 days with simvastatin and 11.5+/-10.4 days with placebo; mean difference, 1.1 days [95% CI, −0.6 to 2.8]; P=0.21). The change from baseline to day 28 in the oxygenation index did not differ significantly between the two groups, nor did the Sequential Organ Failure Assessment (SOFA) score. There were no significant differences in the number of days free of nonpulmonary organ failure or in mortality at 28 days. Mortality at ICU discharge or hospital discharge was also not significantly different between the two groups.
Morning Report Questions
Q: What were the study results with respect to simvastatin’s safety in this clinical setting?
A: Overall, adverse events related to the study drug were significantly more common in the simvastatin group than in the placebo group. The majority of the adverse events were related to elevated creatine kinase and hepatic aminotransferase levels. The numbers of serious adverse events (other than those reported as trial outcomes, such as death) were similar in the two groups. There was no significant between-group difference in the proportion of patients with nonpulmonary organ dysfunction, as measured by a SOFA score of less than 2 for each organ.
Q: How do study results compare with those of the recent Statins for Acutely Injured Lungs from Sepsis (SAILS) study?
A: The recent SAILS study, which involved patients with sepsis-associated ARDS, showed that rosuvastatin did not improve clinical outcomes, as compared with placebo, and was associated with fewer days free of renal and hepatic failure. The authors note that the data from the current study and the SAILS trial show that neither a lipophilic statin (simvastatin) nor a hydrophilic statin (rosuvastatin) is effective in the treatment of ARDS.