Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort

Abstract

Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV1 progression in current smokers. Is use of ACEi and ARB associated with less progression of emphysema and FEV1 decline among individuals with COPD or baseline emphysema? Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume<-950 Hounsfield units [HU]), 15th percentile of the attenuation histogram (attenuation [in HU] below which 15%of voxels are situated plus 1,000 HU), and lung function decline over 5 years between ACEi and ARB users and nonusers in those with spirometry-confirmed COPD, as well as all participants and those with baseline emphysema. Effect modification by smoking status also was investigated. Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95%CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV1 %predicted, 0.83; 95%CI, -0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV1 %predicted, 1.9; 95%CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema. Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline. ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.