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Effect of Statin Therapy on Mortality in Patients with Ventilator-Associated Pneumonia Oral presentation
Original Investigation
Caring for the Critically Ill Patient
October 23/30, 2013

Effect of Statin Therapy on Mortality in Patients With Ventilator-Associated Pneumonia: A Randomized Clinical Trial

Author Affiliations
  • 1Assistance Publique–Hôpitaux de Marseille, Hôpital Nord, Réanimation des Détresses Respiratoires et des Infections Sévères UMR-CNRS 7278, Aix-Marseile Université, Marseille, France
  • 2CHU de Dijon, Service de réanimation médicale, Dijon, France
  • 3Assistance Publique - Hôpitaux de Marseille, Hôpitaux Sud, Pharmacie des Hôpitaux Sud, Marseille, France
  • 4Assistance Publique–Hôpitaux de Marseille, Hôpital de la Timone, Réanimation des Urgences et Médicale, Marseille, France
  • 5Centre Hospitalier de Perpignan, Service de Réanimation, Perpignan, France
  • 6Hôpital d’Instruction des Armées, Hôpital Sainte-Anne, Service de réanimation, Toulon, France
  • 7CHU de Nimes, service des réanimations, Division anesthésie, réanimation, douleur, urgence, Nîmes, France
  • 8Assistance Publique - Hôpitaux de Marseille, Hôpital Nord, Réanimation polyvalente, Marseille, France
  • 9Départment d’Anesthésie Réanimation Saint Eloi, Centre Hospitalier Université de Montellier et Institut National de la Santé et de la Recherche Médicale U-1046 (INSERM U-1046), Montpellier, France
  • 10Hôpital Estaing, Service de réanimation adulte, Clermont-Ferrand, France
  • 11Hospices Civils de Lyon, Hôpital Edouard-Herriot, Service de réanimation médicale, Lyon, France
  • 12Hôpital d’Instruction des Armées, Hôpital Laveran, Service de réanimation, Marseille, France
  • 13Centre Hospitalier d’Aix-en-Provence, Service de réanimation, Aix-en-Provence, France
  • 14Hôpital Ambroise Paré, Service de réanimation, Marseille, France
  • 15Unité d’Aide Méthodologique à la Recherche Clinique–Assistance Publique–Hôpitaux de Marseille; Aix-Marseille Université, Faculté de médecine, Marseille, France
  • 16CIC-Centre de Pharmacologie Clinique et d’Evaluations Thérapeutiques; Hôpital de la Timone, Assistance Publique–Hôpitaux de Marseille, Marseille, France
JAMA. 2013;310(16):1692-1700. doi:10.1001/jama.2013.280031

Importance  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.

Objective  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.

Interventions  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.

Results  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 VAP outcomes.

Trial Registration  clinicaltrials.gov Identifier: NCT01057758