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ABSTRACT & COMMENTARY
By David J. Pierson, MD, Editor
SYNOPSIS: Although studies in animals and preliminary reports in patients with ARDS suggested that statin administration might be beneficial in patients with the syndrome, this multicenter, double-blind clinical trial showed no benefit from simvastatin by any measure examined.
SOURCE: McAuley DF, et al. Simvastatin in the acute respiratory distress syndrome. N Engl J Med 2014;371:1695-1703.
To obtain better evidence about the recent suggestion that statins might be beneficial in managing patients with the acute respiratory distress syndrome (ARDS), McAuley and colleagues carried out a rigorous clinical trial in the ICUs of 40 hospitals in the United Kingdom and Ireland. Mechanically ventilated patients with ARDS (diagnosed using current consensus criteria) who were within 48 hours of syndrome onset and were not already receiving statins were randomized to receive simvastatin, 80 mg, or placebo, enterally, daily for up to 28 days. Clinical outcomes examined were ventilator-free days to day 28, days free of non-pulmonary organ failure, mortality, and safety.
Of the 539 patients (mean age 54 years, 56% male, 75% with sepsis as underlying predisposition), 259 received simvastatin and 280 received placebo. The groups were well matched. No significant differences were found in ventilator-free days (mean, 12.6 vs 11.5 days in statin vs placebo groups), days free of non-pulmonary organ failure (19.4 vs 17.8), 28-day mortality (22% vs 27%), or incidence of serious adverse effects related to the study drug. The authors concluded that simvastatin therapy, although safe, did not improve clinical outcomes in patients with ARDS.
Despite biological plausibility and promising findings in early-phase clinical trials of statins for treatment of ARDS, these things have not translated into improvements in patient-centered outcomes once subjected to rigorous clinical research. This is unfortunate given the ready availability and favorable safety profiles of these agents. Statin therapy can thus be added to the list of management interventions for ARDS that, while initially promising, have ultimately been demonstrated to be ineffective or even harmful. Although manuscripts describing negative clinical trials have tended to be less attractive to journal editors than reports of benefit in anecdotal observations or highly preliminary studies, the former are more important in the long run, once such initial reports have been disseminated, with respect to variables that patients care about.