Adding a statin to antibiotic therapy does not improve survival in critically ill patients with ventilator-associated pneumonia (VAP), according to data from a large randomized controlled trial published online October 9 in JAMA.
In an interim analysis of data from 300 patients, Laurent Papazian, MD, PhD, from Hôpital Nord in Marseille, France, and colleagues found no significant difference in 28-day mortality rate between those taking simvastatin 60 mg or placebo (21.2% vs 15.2%; P = .10). The study was halted for futility, and no additional patients were enrolled.
Although prior studies have suggested a potential survival benefit for statins in sepsis and other severe infections, most of the evidence is observational and confounded by data from patients already receiving the lipid-lowering therapy. In the current study, all but 7% of patients in the simvastatin group and 11% in the placebo group were statin-naive at the time of admission.
"Infection generally, and VAP specifically, represent important causes of morbidity and mortality in critically ill patients. Novel nonantibiotic treatments are urgently needed, and the anti-inflammatory properties of statins have presented an appealing option," noted Andrew F. Shorr, MD, MPH, FCCP, in an interview with Medscape Medical News.
"The current large multicenter [randomized controlled trial] in VAP, however, provides strong evidence that statins are not helpful. These researchers completed a rigorous study focusing on a population at high risk for death and saw no benefit with statins. The fact that the trial was stopped early for futility underscores that statins should not be employed as adjunctive therapy," Dr. Shorr emphasized.
Dr. Shorr is associate chief of the Department of Pulmonary and Critical Care Medicine at Washington Hospital Center and associate professor of medicine in the Department of Pulmonary and Critical Care Medicine at Georgetown University in Washington, DC.
For the study, investigators enrolled consecutive patients in 26 French intensive care units (ICUs) from January 2010 to March 2013 who had received at least 2 days of mechanical ventilation. Probable VAP was diagnosed in 73% of the simvastatin-treated patients and 76% of those receiving placebo.
"Readers should note that nearly 40% of the population was on vasopressors at enrolment and the diagnosis of probable VAP was rigorously defined and established based on lower airway cultures," Dr. Shorr pointed out.
Restricting the analysis to patients with probable VAP did not change the findings: 28-day mortality was 22.6% (95% confidence interval [CI], 15.7% - 31.5%) with simvastatin compared with 14.3% (95% CI, 8.9% - 22.2%) for placebo (P = .06; between-group difference, 8.3% [95% CI, −2.2% to 18.7%]).
Focusing on the subgroup of statin-naive patients likewise failed to show any simvastatin-related survival benefit: 28-day mortality was 21.5% (95% CI, 15.4% - 29.1%) compared with 13.8% (95% CI, 8.8% - 21.0%) for placebo (P = .054; between-group difference, 7.7% [95% CI, −1.8% to 16.8%]).
No significant difference between groups was observed with respect to secondary outcomes, including mortality rates at day 14, in the ICU, or in the hospital; duration of mechanical ventilation; number of ventilator-free days by day 28; number of antibiotic-free days; coronary events; acute respiratory distress syndrome within 28 days of enrolment; changes in sequential organ failure assessment scores on days 3, 7, and 14; or the development of kidney dysfunction.
"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 conclude.
The study was supported by a grant from the French Ministry of Health. Dr Papazian reported receiving payment for providing expert testimony from Faron and receiving travel expenses from Air Liquide Santé. One coauthor reported receiving travel expenses from Fresenius Kabi and MSD. One coauthor reported receiving payment for lectures from Merck France and Pfizer. One coauthor reported receiving travel expenses from Gilead and MSD. The other authors and Dr. Shorr have disclosed no relevant financial relationships.
JAMA. Published online October 9, 2013. Full text
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Cite this: Statin Fails in ICU Pneumonia Trial - Medscape - Oct 14, 2013.