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Statins as adjunct therapy in COPD: how do we cope after STATCOPE?
  1. Robert P Young1,
  2. Raewyn J Hopkins1,
  3. Alvar Agusti2
  1. 1School of Biological Science and the Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
  2. 2Thorax Institute, Hospital Clinic, IDIBAPS, University of Barcelona, and CIBERES, Madrid, Spain
  1. Correspondence to Dr RP Young, University of Auckland, P.O. Box 26161 Epsom, Auckland 1344, New Zealand; roberty{at}adhb.govt.nz.

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Introduction

Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase that are widely used to reduce cardiovascular (CVS) disease risk yet have pleiotropic effects in other organs, including the lungs.1 ,2 The results of the Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE) study, that investigated their potential effects on exacerbations of COPD, have been recently published in the New England Journal of Medicine.3 In this Hot off the breath editorial, we review the rationale for the study, discuss its design, main results, strengths and limitations, and speculate on the future of statins in COPD.

Rationale: hints from observational studies

Statins reduce the recruitment of neutrophils and macrophages into the lung, alter bronchial remodelling, prevent emphysema and reduce systemic inflammation.1 ,2 ,4 These biological effects appear to have clinical relevance as observational studies in COPD patients report reduced all-cause mortality,5–8 reduced mortality from acute exacerbations,8–10 reduced frequency of COPD exacerbations,8 ,11–13 and reduced decline of lung function,14 for those taking statins, as compared to not taking them.

In one small randomised controlled trial (RCT), statin use in COPD patients was associated with a clinically significant increase in exercise tolerance, although this benefit was limited to those in whom baseline C-reactive protein (CRP) was elevated (ie, those with evidence of systemic inflammation).15 To date, STATCOPE is the only RCT that has assessed the effect of adjunct statin treatment prospectively on acute exacerbations in COPD in a large cohort of patients.3

STATCOPE findings: the basis of discordant results

STATCOPE was a large, randomised, multicentre, double-blind, placebo-controlled trial of simvastatin (40 mg/day) in the prevention of COPD exacerbations in patients with moderate-to-severe COPD (N=885).3 Importantly, patients with diabetes or CVS disease (figure 1), those already on statins, or those that required statins based on accepted CVS risk criteria, were excluded. The …

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