Medical News Stories
Effect of Statin Therapy on Mortality in Patients with Ventilator-Associated Pneumonia: a Randomized Clinical Trial
Study Question: Does adjunctive statin therapy decrease 28-day mortality among ICU patients with ventilator-associated pneumonia (VAP).
Study Description: This was a 1:1 randomized, parallel-group, placebo-controlled, double-blind trial in 26 French ICUs. Adults who had received mechanical ventilation in the ICU for at least two days and had suspected VAP were randomly assigned to simvastatin (60 mg) or placebo given via nasogastric tube or orally from study inclusion to ICU discharge, death, or day 28, whichever occurred first. Simvastatin or placebo was started on the same day as antibiotic therapy for suspected VAP.
Results: Three hundred patients were enrolled between January 2012 and December 2012; 146 patients in the simvastatin group and 138 patients in the placebo group. The only baseline difference between the groups was a higher proportion of patients receiving antibiotics prior to enrollment in the simvastatin group. Only 7% of patients in the simvastatin group and 11% of patients in the placebo group received statins during the month prior to enrollment. Simvastatin or placebo was started within 24 hours after the first dose of antibiotics prescribed for VAP. A majority of patients had probable VAP and there were no between-group differences in rates of multidrug-resistant organisms.
The trial was stopped for futility at the first scheduled interim analysis; simvastatin did not significantly decrease 28-day mortality compared to placebo (21.2% vs. 15.2%, respectively, p = 0.10). In patients who were naïve to statins, 28-day mortality was 21.5% with simvastatin and 13.8% with placebo (p = 0.054). After adjustment, simvastatin was not significantly associated with 28-day mortality. There was no significant difference in 14-day, ICU, or hospital mortality, mechanical ventilation duration, number of ventilator free days by day 28, coronary events, or incidence of acute respiratory distress syndrome within 28 days of enrollment. Simvastatin was well tolerated, with no increases in rates of elevated creatine kinase, ALT, or AST levels. There were also no unexpected adverse reactions during the study.
Conclusion(s): Simvastatin therapy did not improve day-28 survival in adults with suspected VAP.
Perspective: Although several studies have been conducted evaluating the use of statins in sepsis, community-acquired pneumonia, and other severe infections, this is the first randomized, placebo-controlled trial evaluating clinical outcomes in an ICU population with VAP. Although the rate of mortality was not significantly different between the two groups, the study was stopped early due to the increased rate of mortality in the simvastatin group. Based on these results, simvastatin should not be used as an adjunct to improve outcomes in ICU patients with VAP at the present time.