Performance of statin therapy in reducing the death rate of pneumonia patients in intensive care units was so poor that a study was stopped for futility.
Although previous research has linked statins with improved outcomes for multiple infections, the results of a new study find that statin therapy in addition to treatment with antibiotics may not reduce the risk of death in patients with ventilator-associated pneumonia.
Data from prior observational studies have suggested that statin therapy is beneficial in treating sepsis and non-severe infections, but evidence regarding its benefit in treating community-acquired pneumonia has been inconsistent and conflicting. The current randomized trial, published
in the October 23/30 issue of the Journal of the American Medical Association
, analyzed the efficacy of statins in reducing the day-28 mortality rate of pneumonia patients requiring invasive mechanical ventilation in 26 intensive care units (ICU) in France from January 2010 to March 2013.
Patients were suspected of having ventilator-associated pneumonia if they had a Clinical Pulmonary Infection Score of at least 5 and underwent quantitative bacteriological cultures of bronchoalveolar lavage fluid, a protected telescopic catheter, or an endotracheal aspirate. These patients were eligible for the trial if they required mechanical ventilation for at least 2 days. Participants were randomized to receive 60 mg of simvastatin or a placebo given orally or through a nasogastric tube. Statin or placebo therapy was initiated at the same time as antibiotic therapy and continued until discharge, day 28, or death, whichever occurred first.
The researchers planned to enroll more than 1000 patients, but only 300 patients were enrolled before the trial was stopped for futility. Only 7% of patients in the simvastatin group and 11% of placebo patients had been taking statins before joining the study. All of these patients had stopped taking statins upon admission to the ICU. The results indicated that simvastatin did not reduce day-28 mortality when compared with placebo. After 28 days, the mortality rate was 21.2% among statin patients and 15.2% among placebo patients. However, the difference in mortality rates between the groups was not statistically significant. Results were similar in a secondary analysis excluding those patients who had been taking statins prior to joining the study. Simvastatin also had no significant effect on day-14 ICU or hospital mortality rates, ventilation duration, the number of ventilator-free days at day 28, acute respiratory distress syndrome, or coronary events when compared with placebo.
The authors of the study note that because the trial was ended early, it is possible that statin therapy has small, long-term benefits in treating ventilator-associated pneumonia. Nonetheless, they recommend against statin use in these patients. “Our results do not support the use of adjunctive statin therapy in ICU patients with [ventilator-associated pneumonia], and this conclusion probably deserves to be extended to ICU patients with any type of nosocomial infection,” they write.