Observational studies have reported that statin use may be associated with improved outcomes of
various infections. Ventilator-associated pneumonia (VAP) is the most common infection in the
intensive care unit (ICU) and is associated with substantial mortality.
To determine whether statin therapy can decrease day-28 mortality in patients with VAP.
Design, Setting, and Participants
Randomized, placebo-controlled, double-blind, parallel-group, multicenter trial performed in 26
intensive care units in France from January 2010 to March 2013. For power to detect an 8% absolute
reduction in the day-28 mortality rate, we planned to enroll 1002 patients requiring invasive
mechanical ventilation for more than 2 days and having suspected VAP, defined as a modified Clinical
Pulmonary Infection Score of 5 or greater. The futility stopping rules were an absolute increase in
day-28 mortality of at least 2.7% with simvastatin compared with placebo after enrollment of the
first 251 patients.
Participants were randomized to receive simvastatin (60 mg) or placebo, started on the same day
as antibiotic therapy and given until ICU discharge, death, or day 28, whichever occurred first.
Main Outcomes and Measures
Primary outcome was day-28 mortality. Day-14, ICU, and hospital mortality rates were determined,
as well as duration of mechanical ventilation and Sequential Organ Failure Assessment (SOFA) scores
on days 3, 7, and 14.
The study was stopped for futility at the first scheduled interim analysis after enrollment of
300 patients, of whom all but 7% in the simvastatin group and 11% in the placebo group were naive to
statin therapy at ICU admission. Day-28 mortality was not lower in the simvastatin group (21.2% [95%
CI, 15.4% to 28.6%) than in the placebo group (15.2% [95% CI, 10.2% to 22.1%];
P = .10; hazard ratio, 1.45 [95% CI, 0.83 to 2.51]); the between-group
difference was 6.0% (95% CI, −3.0% to 14.9%). In statin-naive patients, day-28 mortality was
21.5% (95% CI, 15.4% to 29.1%) with simvastatin and 13.8% (95% CI, 8.8% to 21.0%) with placebo
(P = .054) (between-group difference, 7.7% [95%CI, −1.8% to
16.8%). There were no significant differences regarding day-14, ICU, or hospital mortality rates;
duration of mechanical ventilation; or changes in SOFA score.
Conclusions and Relevance
In adults with suspected VAP, adjunctive simvastatin therapy compared with placebo did not
improve day-28 survival. These findings do not support the use of statins with the goal of improving
clinicaltrials.gov Identifier: NCT01057758