ARTICLE: Emphysema progression and lung function decline among angiotensin converting enzyme inhibitors (ACEi) and angiotensin-receptor blockade (ARB) users in the COPDGene® Cohort

AUTHORS: Vickram TejwaniAshraf FawzyNirupama Putcha, Peter Castaldi, Michael H Cho, Katherine A Pratte, Surya P Bhatt, David A Lynch, Stephen M Humphries, Gregory L Kinney, Franco R D'AlessioNadia N Hansel

JOURNAL: Chest. 2021 May 21;S0012-3692(21)00898-9. doi: 10.1016/j.chest.2021.05.007. Online ahead of print.

Abstract

Background: 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 use of angiotensin converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARBs) are associated with reduction of emphysema progression in former smokers and ACEi with reduction of FEV1 progression in current smokers.

Research question: Is ACEi/ARB use associated with less progression of emphysema and FEV1 decline among individuals with COPD or baseline emphysema?

Methods: Former and current smokers from the COPDGene® study who attended baseline and 5-year follow-up visits, did not change smoking status, and had chest CT performed were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (% TLV <-950 HU), Perc15 (attenuation [in HU] below which 15% of voxels are situated + 1000 HU), and lung function decline over five years between ACEi/ARB-users and non-users in those with spirometry confirmed COPD, as well as all participants and those with baseline emphysema. Effect modification by smoking status was also investigated. This study is registered at ClinicalTrials.gov (NCT00608764).

Results: Over 5-year follow-up, compared to non-users, ACEi/ARB users with COPD had slower ALD progression (adjusted mean difference [aMD]: 1.6, 95% confidence interval [95%CI]: 0.34, 2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV1 percent predicted: 0.83, 95%CI: -0.62, 2.3) but was when analysis was limited to consistent ACEi/ARB users (aMD of FEV1 percent predicted: 1.9, 95%CI: 0.14, 3.6). There was no effect modification by smoking status for radiographic outcomes and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema.

Interpretation: Among participants with spirometry confirmed COPD or baseline emphysema, ACEi/ARB use was associated with slower progression of emphysema and lung function decline.

Keywords: COPD; angiotensin II; emphysema progression.

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