title: Statin therapy for acute respiratory distress syndrome: an individual patient data meta-analysis of randomised clinical trials.
abstract: OBJECTIVE
  We performed an individual patient data meta-analysis to assess the possible benefits and harms of statin therapy in adults with acute respiratory distress syndrome (ARDS) and to investigate effects in specific ARDS subgroups.
  
  
  METHODS
  We identified randomised clinical trials up to 31 October 2016 that had investigated statin therapy versus placebo in patients with ARDS. Individual patient data from each trial were compiled. Conventional two-stage meta-analyses were performed for primary and secondary outcomes, and one-stage regression models with single treatment-covariate interactions for subgroup analyses. Risk of bias was assessed using the Cochrane Risk of Bias Tool.
  
  
  RESULTS
  Six trials with a total of 1755 patients were included. For the primary outcomes, there was no significant effect of statin therapy on 28-day mortality [relative risk (RR) 1.03, 95% CI 0.86-1.23], ventilator-free days (mean difference 0.34 days, 95% CI -0.68 to 1.36) or serious adverse events (RR 1.14, 95% CI 0.84-1.53). There was a significantly increased incidence of raised serum creatine kinase or transaminase levels with statin therapy (106/879; 12.1%) versus control (78/876; 8.9%) (RR 1.40, 95% CI 1.07-1.83, p = 0.015). There were no significant treatment-covariate interactions in the predefined subgroups investigated.
  
  
  CONCLUSIONS
  We found no clinical benefit from initiation of statin therapy in adult patients with ARDS, either overall or in predefined subgroups. While there was an increased incidence of raised serum creatine kinase and transaminase levels, there was no difference in serious adverse events among groups. Therefore, we do not recommend initiation of statin therapy for the treatment of ARDS.
authors.affiliation: Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London and Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, UK.
authors.forename: Myura
authors.initials: M
authors.lastname: Nagendran
authors.affiliation: School of Medicine, Dentistry and Biomedical Sciences, Queen's University of Belfast, Belfast, UK.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: McAuley
authors.affiliation: Princess Alexandra Hospital, Metro South Health, Woolloongabba, QLD, Australia.|School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Kruger
authors.affiliation: Medical Intensive Care Unit, North Hospital, Aix-Marseille University, Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Papazian
authors.affiliation: Pulmonary and Critical Care Medicine, Froedtert and Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Jonathon D
authors.initials: JD
authors.lastname: Truwit
authors.affiliation: Departments of Anesthesia and Critical Care Medicine, St Michael's Hospital, University of Toronto, Toronto, Canada.
authors.forename: John G
authors.initials: JG
authors.lastname: Laffey
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: B Taylor
authors.initials: BT
authors.lastname: Thompson
authors.affiliation: School of Medicine, Dentistry and Biomedical Sciences, Queen's University of Belfast, Belfast, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Clarke
authors.affiliation: Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London and Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, UK. anthony.gordon@imperial.ac.uk.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Gordon
mesh_terms: D000328:Adult; D003402:Creatine Kinase / Q000097:blood; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D000637:Transaminases / Q000097:blood; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000637:Transaminases; D003402:Creatine Kinase
keywords: ALI; ARDS; Meta-analysis; Statin