Intensive Care Medicine

, Volume 43, Issue 5, pp 663–671 | Cite as

Statin therapy for acute respiratory distress syndrome: an individual patient data meta-analysis of randomised clinical trials

  • Myura Nagendran
  • Daniel F. McAuley
  • Peter S. Kruger
  • Laurent Papazian
  • Jonathon D. Truwit
  • John G. Laffey
  • B. Taylor Thompson
  • Mike Clarke
  • Anthony C. GordonEmail author
Systematic Review



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.


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.


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.


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.


Statin ARDS ALI Meta-analysis 



We are grateful to the investigators and clinical trials groups of all the trials included in this study for providing access to their trial data. ACG is grateful for support from the National Institute for Health Research Comprehensive Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. ACG and DFM are grateful for support from the UK Intensive Care Foundation.

Compliance with ethical standards


There was no specific funding for this study. The HARP2 trial was supported by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership (08/99/08). The EME Programme is funded by the MRC and NIHR, with contributions from the Chief Scientist Office (CSO) in Scotland and National Institute for Social Care and Health Research (NISCHR) in Wales and the Health & Social Care (HSC) R&D Division, Public Health Agency in Northern Ireland. The views expressed in this publication are those of the authors and not necessarily those of the MRC, NHS, NIHR or the Department of Health.

Conflicts of interest

DMcA reports Grants from the National Institute for Health Research, Efficacy and Mechanism Evaluation, the Health Research Board, Health and Social Care Research & Development office, the Intensive Care Society Ireland, and REVIVE to support the conduct of HARP-2. Outside the submitted work, DMcA reports personal fees from consultancy for GlaxoSmithKline (GSK), SOBI, Bayer, Boehringer Ingelheim and Peptinnovate. His institution has received grants from the NIHR and others, as well as funds from GSK for DMcA undertaking bronchoscopy as part of a clinical trial. In addition, DMcA also holds a patent for the use of a pharmacotherapy (not a statin) for treatment of ARDS awarded to Queen’s University Belfast. BTT reports Grants from the National Heart, Lung, and Blood Institute of the National Institute of Health. Outside the submitted work, BTT reports personal fees from consultancy for Alexion, Asahi Kasei, Boehringer Ingelheim, GlaxoSmithKline, and Regeneron. ACG reports, outside the submitted work, grants from the National Institute for Health Research that he has received speaker fees from Orion Corporation Orion Pharma and Amomed. He has consulted for Ferring Pharmaceuticals, Tenax Therapeutics and received Grant support from Orion Corporation Orion Pharma, Tenax Therapeutics and HCA International with funds paid to his institution. Other authors declare that they have no conflicts of interest.

Supplementary material

134_2016_4649_MOESM1_ESM.docx (777 kb)
Supplementary material 1 (DOCX 776 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2016

Authors and Affiliations

  • Myura Nagendran
    • 1
  • Daniel F. McAuley
    • 2
  • Peter S. Kruger
    • 3
    • 8
  • Laurent Papazian
    • 4
  • Jonathon D. Truwit
    • 5
  • John G. Laffey
    • 6
  • B. Taylor Thompson
    • 7
  • Mike Clarke
    • 2
  • Anthony C. Gordon
    • 1
    Email author
  1. 1.Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and CancerImperial College London and Charing Cross HospitalLondonUK
  2. 2.School of Medicine, Dentistry and Biomedical SciencesQueen’s University of BelfastBelfastUK
  3. 3.Princess Alexandra HospitalMetro South HealthWoolloongabbaAustralia
  4. 4.Medical Intensive Care UnitNorth Hospital, Aix-Marseille UniversityMarseilleFrance
  5. 5.Pulmonary and Critical Care MedicineFroedtert and Medical College of WisconsinMilwaukeeUSA
  6. 6.Departments of Anesthesia and Critical Care MedicineSt Michael’s Hospital, University of TorontoTorontoCanada
  7. 7.Division of Pulmonary and Critical Care MedicineMassachusetts General Hospital and Harvard Medical SchoolBostonUSA
  8. 8.School of MedicineUniversity of QueenslandBrisbaneAustralia

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