Simvastatin in the Acute Respiratory Distress Syndrome

Daniel F. McAuley, John G. Laffey, Cecilia M. O'Kane, Gavin D. Perkins, Brian Mullan, T. John Trinder, Paul Johnston, Philip A. Hopkins, Andrew J. Johnston, Cliona McDowell, Christine McNally, the HARP-2 Investigators, for the Irish Critical Care Trials Group

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Abstract

Background

Studies in animals and in vitro and phase 2 studies in humans suggest that statins may be beneficial in the treatment of the acute respiratory distress syndrome (ARDS). This study tested the hypothesis that treatment with simvastatin would improve clinical outcomes in patients with ARDS.

Methods

In this multicenter, double-blind clinical trial, we randomly assigned (in a 1:1 ratio) patients with an onset of ARDS within the previous 48 hours to receive enteral simvastatin at a dose of 80 mg or placebo once daily for a maximum of 28 days. The primary outcome was the number of ventilator-free days to day 28. Secondary outcomes included the number of days free of nonpulmonary organ failure to day 28, mortality at 28 days, and safety.

Results

The study recruited 540 patients, with 259 patients assigned to simvastatin and 281 to placebo. The groups were well matched with respect to demographic and baseline physiological variables. There was no significant difference between the study groups in the mean (±SD) number of ventilator-free days (12.6±9.9 with simvastatin and 11.5±10.4 with placebo, P=0.21) or days free of nonpulmonary organ failure (19.4±11.1 and 17.8±11.7, respectively; P=0.11) or in mortality at 28 days (22.0% and 26.8%, respectively; P=0.23). There was no significant difference between the two groups in the incidence of serious adverse events related to the study drug.

Conclusions

Simvastatin therapy, although safe and associated with minimal adverse effects, did not improve clinical outcomes in patients with ARDS. (Funded by the U.K. National Institute for Health Research Efficacy and Mechanism Evaluation Programme and others; HARP-2 Current Controlled Trials number, ISRCTN88244364.)


Original languageEnglish
Pages (from-to)1695-1703
JournalNew England Journal of Medicine
Volume371
DOIs
Publication statusPublished - 30 Oct 2014

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  • Cite this

    McAuley, D. F., Laffey, J. G., O'Kane, C. M., Perkins, G. D., Mullan, B., Trinder, T. J., Johnston, P., Hopkins, P. A., Johnston, A. J., McDowell, C., McNally, C., & the HARP-2 Investigators, for the Irish Critical Care Trials Group (2014). Simvastatin in the Acute Respiratory Distress Syndrome. New England Journal of Medicine, 371, 1695-1703. https://doi.org/10.1056/NEJMoa1403285