We used simvastatin at a dose of 80 mg on the basis of our previous data from clinical studies,4,5 in which simvastatin improved surrogate outcomes and biologic mechanisms implicated in ARDS. The data from our 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. The high dose of simvastatin (80 mg) used in this trial was selected on the basis of our pilot data5 as well as preclinical data3 and observational studies.13,14 Although we did not measure simvastatin concentrations, it is likely that an adequate simvastatin concentration was achieved, for several reasons. A prior study involving critically ill patients showed that simvastatin at a daily dose of 80 mg produced systemic drug concentrations that were in the high therapeutic range.15 Furthermore, patients received simvastatin for a mean of 10 days. Finally, the increased incidence of expected statin-related adverse events suggests that sufficient simvastatin concentrations were achieved. The lack of an effect on the plasma C-reactive protein level suggests that statins cannot modulate inflammation sufficiently to provide a beneficial clinical effect in ARDS. It is possible that HMG-CoA reductase is already substantially inhibited, as reflected by the low cholesterol levels seen in critically ill patients.16