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Original article
Effect of statins on disease-related outcomes in patients with idiopathic pulmonary fibrosis
  1. Michael Kreuter1,2,
  2. Francesco Bonella3,
  3. Toby M Maher4,
  4. Ulrich Costabel3,
  5. Paolo Spagnolo5,
  6. Derek Weycker6,
  7. Klaus-Uwe Kirchgaessler7,
  8. Martin Kolb8
  1. 1Center for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Critical Care Medicine, Thoraxklinik, University of Heidelberg, and Translational Lung Research Center Heidelberg (TLRCH), Heidelberg, Germany
  2. 2Member of the German Center for Lung Research (DZL), Heidelberg, Germany
  3. 3Interstitial and Rare Lung Disease Unit, Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Essen, Germany
  4. 4NIHR Biomedical Research Unit, Royal Brompton Hospital, London, UK
  5. 5Section of Respiratory Diseases, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy
  6. 6Policy Analysis Inc. (PAI), MINERVA Health Economics Network, Ltd., Brookline, Massachusetts, USA
  7. 7F. Hoffmann-La Roche Ltd, Basel, Switzerland
  8. 8Department of Medicine, Pathology & Molecular Medicine, Firestone Institute for Respiratory Health, McMaster University, Hamilton, Ontario, Canada
  1. Correspondence to Dr Michael Kreuter, Center for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Critical Care Medicine, Thoraxklinik, Heidelberg University Hospital, Röntgenstrasse 1, Heidelberg 69120, Germany; kreuter{at}uni-heidelberg.de

Abstract

Background Data are conflicting regarding the possible effects of statins in patients with idiopathic pulmonary fibrosis (IPF). This post hoc analysis assessed the effects of statin therapy on disease-related outcomes in IPF.

Methods Patients randomised to placebo (n=624) in three controlled trials of pirfenidone in IPF (CAPACITY 004 and 006, ASCEND) were categorised by baseline statin use. Outcomes assessed during the 1-year follow-up included disease progression, mortality, hospitalisation and composite outcomes of death or ≥10% absolute decline in FVC and death or ≥50 m decline in 6-minute walk distance (6MWD).

Results At baseline, 276 (44%) patients were statin users versus 348 (56%) non-users. Baseline characteristics were similar between groups, except statin users were older and had higher prevalence of cardiovascular disease and risk factors. In multivariate analyses adjusting for differences in baseline characteristics, statin users had lower risks of death or 6MWD decline (HR 0.69; 95% CI 0.48 to 0.99, p=0.0465), all-cause hospitalisation (HR 0.58; 95% CI 0.35 to 0.94, p=0.0289), respiratory-related hospitalisation (HR 0.44; 95% CI 0.25 to 0.80, p=0.0063) and IPF-related mortality (HR 0.36; 95% CI 0.14 to 0.95, p=0.0393) versus non-users. Non-significant treatment effects favouring statin use were observed for disease progression (HR 0.75; 95% CI 0.52 to 1.07, p=0.1135), all-cause mortality (HR 0.54; 95% CI 0.24 to 1.21, p=0.1369) and death or FVC decline (HR 0.71; 95% CI 0.48 to 1.07, p=0.1032).

Conclusions This post hoc analysis supports the hypothesis that statins may have a beneficial effect on clinical outcomes in IPF. Prospective clinical trials are required to validate these observations.

Trial registration numbers NCT01366209, NCT00287729 and NCT00287716.

  • Idiopathic pulmonary fibrosis

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Footnotes

  • Contributors MKr, MKo and DW were involved in the design of the analysis. DW was involved in the execution of the analysis. All authors were involved in the interpretation of the results. All authors were involved in drafting and revising this manuscript, and provided final approval of the version to be published. All authors vouch for the accuracy of the content included in the final manuscript.

  • Funding The sponsor, F. Hoffmann-La Roche, funded the analysis of the data by Policy Analysis Inc. (PAI). Programming support was provided by Mark Atwood of Policy Analysis Inc. (PAI). Medical writing support was provided by Dr Tracey Lonergan on behalf of Complete Medical Communications Ltd, funded by F. Hoffmann-La Roche Ltd.

  • Competing interests MKr and his institution have received unrestricted grants and personal fees from InterMune International AG which became a wholly owned subsidiary of Roche in 2014, F. Hoffmann-La Roche Ltd and Boehringer Ingelheim. FB has received speaker fees, advisory board honoraria or grants from InterMune International AG which became a wholly owned subsidiary of Roche in 2014, Boehringer Ingelheim, Gilead, Serendex, Centocor and F. Hoffmann-La Roche Ltd. TMM is supported by a National Institute for Health Research Clinician Scientist Fellowship (NIHR Ref: CS:-2013-13-017). He has received research grants from GlaxoSmithKline, UCB and Novartis; and consulting and speaker fees from AstraZeneca, Bayer, Biogen Idec, Boehringer Ingelheim, Cipla, Dosa, GlaxoSmithKline, Lanthio, InterMune International AG which became a wholly owned subsidiary of Roche in 2014, F. Hoffmann-La Roche Ltd, Sanofi-Aventis, Takeda and UCB. UC has received grants, personal fees and non-financial support from Boehringer Ingelheim. He has received grants, personal fees and non-financial support from Intermune International AG which became a wholly owned subsidiary of Roche in 2014, and personal fees from F. Hoffmann-La Roche Ltd, Bayer, Gilead, GlaxoSmithKline, UCB, Biogen and Centocor (all outside the submitted work). PS has received consulting fees from InterMune International AG which became a wholly owned subsidiary of Roche in 2014, F. Hoffmann-La Roche Ltd and Santhera Pharmaceuticals Ltd, and personal fees from Boehringer Ingelheim and Novartis. DW is an employee of Policy Analysis Inc. (PAI), which received funding from F. Hoffmann-La Roche Ltd for this study. K-UK is an employee of F. Hoffmann-La Roche Ltd, Basel, Switzerland. MKo has served as site Principal Investigator in industry-sponsored clinical trials (Centocor, Roche, Sanofi and Boehringer Ingelheim) and is funded by the Canadian Institute for Health Research. He has served and/or serves on the Pulmonary Fibrosis Foundation Medical Advisory Board and on Advisory Boards for Boehringer Ingelheim, Roche Canada, GlaxoSmithKline, AstraZeneca, Vertex, Genoa, Gilead, Janssen and Prometic.

  • Ethics approval Ethics committee/institutional review board approval was obtained from each centre participating in the ASCEND and CAPACITY studies (total of 237 centres) as presented in the primary papers reporting the results of those trials (King et al,9 and Noble et al,10). A full list can be provided if required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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