Statin therapy does not decrease mortality among intensive care unit patients with ventilator-associated pneumonia, according to a clinical trial by French researchers.
Investigators stopped the randomized study for futility after analyzing 28-day mortality results in the first 300 of a projected 1,002 patients, and finding higher rates among patients randomized to take daily simvastatin (21.2%) compared with placebo (15.2%). The study, published online Oct. 8 in JAMA, was released this week at the European Society of Intensive Care Medicine’s annual congress.
"These findings do not support the use of statins with the goal of improving VAP outcomes," wrote the study authors, led by Dr. Laurent Papazian of Hôpital Nord in Marseille, France.
For the trial, conducted in 26 French intensive care units (ICUs) between January 2010 and March 2013, patients who had received mechanical ventilation for at least 2 days were eligible for participation if they had suspected ventilator-associated pneumonia (VAP), defined as a modified Clinical Pulmonary Infection Score of at least 5, and if they had quantitative bacteriological cultures of bronchoalveolar lavage fluid, a protected telescopic catheter, or an endotracheal aspirate.
In a double-blind study, participants were randomized to receive a daily 60-mg dose of simvastatin or placebo given orally or via a nasogastric tube from study inclusion until ICU discharge, death, or day 28, whichever occurred first. Simvastatin or placebo was started on the same day as antibiotic therapy for suspected VAP (JAMA 2013 Oct. 9 [doi: 10.1001/jama.2013.280031]).
A total of 153 patients received simvastatin, and 147 received placebo; all patients received at least one dose. The only clinically significant baseline difference between groups was a higher proportion of patients receiving antibiotics in the simvastatin group. No patients had definite bacterial VAP. Probable VAP was diagnosed in 106 patients (73%) in the simvastatin group and 105 (76%) in the placebo group.
Analyzing 28-day mortality, the investigators found that restricting the analysis to patients with probable VAP did not change the overall results: Day 28 mortality was 22.6% with simvastatin versus 14.3% with placebo.
There were no significant between-group differences in day 14, ICU, or hospital mortality rates; mechanical ventilation duration; number of ventilator-free days by day 28; coronary events; or acute respiratory distress syndrome (ARDS) within 28 days after enrollment. The groups also did not differ regarding the course of organ dysfunctions or the development of kidney dysfunction.
Simvastatin was "well tolerated, with no increases in rates of elevated creatine kinase, ALT or AST levels," the authors noted, and no between-group differences in creatinine levels at days 3, 7, 14, or 21. The study treatment was interrupted for at least 24 hours because of an adverse event in 55 patients (19%) in the simvastatin group and 24 (17%) in the placebo group.
"Our results do not support the use of adjunctive statin therapy in ICU patients with VAP, and this conclusion probably deserves to be extended to ICU patients with any type of nosocomial infection," the authors wrote.
The study was supported by the French Ministry of Health. Four of the 21 authors disclosed receiving travel expenses, payment for lectures, or payment for providing expert testimony from industry sources, including Fresenius Kabi and MSD. No other authors reported disclosures.