Simvastatin in the acute respiratory distress syndrome

TY - JOUR

T1 - Simvastatin in the acute respiratory distress syndrome

AU - McAuley, Daniel F.

AU - Laffey, John G.

AU - O'Kane, Cecilia M.

AU - Perkins, Gavin D.

AU - Mullan, Brian

AU - Trinder, T. John

AU - Johnston, Paul

AU - Hopkins, Philip

AU - Johnston, Andrew J.

AU - McDowell, Cliona

AU - McNally, Christine

PY - 2014/10/30

Y1 - 2014/10/30

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84908434411&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1403285

DO - 10.1056/NEJMoa1403285

M3 - Article

C2 - 25268516

AN - SCOPUS:84908434411

SN - 0028-4793

VL - 371

SP - 1695

EP - 1703

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 18

ER -