Statins In COPD: A Statins In COPD: A Systematic ReviewSystematic ReviewSurinder J, Kirly P et al. Chest 2009; 136: 734-Surinder J, Kirly P et al. Chest 2009; 136: 734-743.743.

Divya BappanadMarch 11, 2010Journal Club

BackgroundBackgroundCOPD is a systemic inflammatory

disease not limited to the lung

Increased recruitment and activation of inflammatory cells( neutrophils, eosinophils, lymphocytes and alveolar macrophages)

Increased levels of IL-6, IL-8, CRP, fibrinogen, TNF, and leukocytes

Chronic inflammation persists even after cessation of smoking

BackgroundBackgroundStatins pleiotropic anti-inflammatory

effects

Decrease neutrophil numbers, T cell activation and differentiation, and increase apoptosis of eosinophils

Also regulate inflammation by increased phagocytosis of apoptotic cells

Murine and rat models demonstrate slowed progression of emphysema with statin use

MethodsMethods

Study Sources – Medline, Cochrane, PapersFirst and Excerpta Medical Database as well as bibliographies of found papers

Design of studies included – randomized, single or double blinded, placebo controlled, observational cohort( prospective or restrospective), population based analysis

Study exclusion criteria – laboratory or experimental based studies

Number of studies screened vs. accepted – 264 vs 9

Outcomes – All cause mortality, COPD related mortality, COPD, the time to and number of COPD exacerbations, the time to an number of COPD intubations, exercise capacity, and pulmonary function FEV1 and FVC

ValidityValidityFocused clinical question addressed

Appropriate study inclusion criteria

No important studies excluded

Significant degree of heterogeneity between studies

ResultsResults4 retrospective cohort

1 nested case control of a retrospective cohort

1 combination retrospective cohort

2 case control

1 randominized controlled trial

ResultsResultsAll cause mortality

◦Mancini et al nested case control OR 0.53(95% CI 0.43 -0.65) vs OR

0.49(95% CI0.41-0.58) In both high risk CV and low risk CV group

◦Soyseth et al retrospective cohort HR 0.57(95% CI 0.38-0.87)

◦Van Gestel et al retrospective cohort short term( 30 day) OR 0.48(95% CI 0.23-

1) long term(10 year) OR (95% CI 0.52-0.86)

ResultsResultsCOPD related mortality

◦Frost et al retrospective cohort and case control Low dose statin OR 0.58(95% CI 0.17-

0.92) Moderate dose statin OR 0.17(95% CI

0.07-0.42) Dose dependant effect

◦Ishida et al population based Annual sales with negative correlation Correlation coefficient 0.574(p<0.001)

ResultsResultsCOPD hospitalizations

◦Keddissi et al retrospective cohort *0.17+/- 0.31 patients per year vs 0.11 +/-

0.26 patients per year But rate decrease FEV1 and FVC slowed with

statin use◦Mancini et al

High risk CV OR 0.71(95% CI 0.56 -0.91) Low risk CV OR 0.71(95% CI 0.64-0.77)

COPD exacerbations◦Blamoun et al retrospective cohort

OR 2.35(95% CI 1.01-5.5)

ResultsResultsExercise capacity and CRP

◦Lee et al RCT ◦Pravastatin vs placebo◦Increased exercise time on treadmill

599 +/- 323 to 922 +/- 328 s p<0.0001

◦Decreased CRP 3.94 +/- 3.54 to 2.66 +/- 2.49 p<0.0005

CommentsCommentsAll studies showed benefit in range of

COPD related outcomes

Clinical finding correlate to findings in pulmonary systems of animal models

Lack of RCTs mean that confounding variables and bias present

Definitions of COPD varied as did dose and duration of statins

Next stepsNext stepsAtorvastatin vs placebo for

change in peak flow

Simvastatin vs placebo for changes in CRP

Lovastatin vs placebo for changes in apoptosis and efferocytosis in pulmonary macrophages