Journal article
Lung Function and the Risk of Exacerbation in the ?-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease Trial
Annals of the American Thoracic Society, Vol.19(10), pp.1642-1649
10/2022
DOI: 10.1513/AnnalsATS.202109-1042OC
PMCID: PMC9528740
PMID: 35363600
Abstract
The BLOCK COPD (β-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease) study found that metoprolol was associated with a higher risk of severe exacerbation.
To determine the mechanism underlying these results, we compared changes in lung function over the course of the study between treatment groups and evaluated whether baseline bronchodilator response or early reduction in forced expiratory volume in 1 second (FEV
) or forced vital capacity (FVC) was associated with exacerbation risk.
We compared changes in lung function (FEV
and FVC) over the treatment period between treatment groups using linear mixed-effect models. Cox proportional hazards models were used to evaluate the association between baseline bronchodilator responsiveness (FEV
, FVC, and combined FEV
and FVC), early post-randomization (14 d) change in lung function, and the interaction between treatment assignment and these measures with risk of any or severe or very severe exacerbations. Negative binomial models were used to evaluate the relationship between bronchodilator responsiveness, the interaction between bronchodilator responsiveness and treatment assignment, and exacerbation rate.
Over the 336-day treatment period, individuals in the metoprolol group had a significantly greater decrease in logarithmic FEV
from baseline to visit on Day 28 than individuals in the placebo group. Individuals in the metoprolol group had a significantly greater decrease in FVC from baseline to visits on Days 14 and 28, and also a significantly greater decrease in logarithmic FVC from baseline to visits on Days 42 and 112 than individuals in the placebo group. There were no associations between early lung function reduction or interactions between lung function reduction and treatment assignment and time to any or severe or very severe exacerbations. There were no interactions between treatment arm and baseline bronchodilator responsiveness measures on risk or rate of exacerbations. However, those with baseline FVC bronchodilator responsiveness had a higher rate of severe or very severe exacerbations (adjusted rate ratio, 1.62; 95% confidence interval, 1.04-2.48).
Metoprolol was associated with reduced lung function during the early part of the treatment period, but these effects were modest and did not persist. Early lung function reduction and baseline bronchodilator responsiveness did not interact with the treatment arm to predict exacerbations; however, baseline FVC bronchodilator responsiveness was associated with a 60% higher rate of severe or very severe exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT02587351).
Details
- Title: Subtitle
- Lung Function and the Risk of Exacerbation in the ?-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease Trial
- Creators
- Trisha M Parekh - University of Alabama at BirminghamErika S Helgeson - University of MinnesotaJohn Connett - University of MinnesotaHelen Voelker - University of MinnesotaSharon X Ling - University of Minnesota SystemStephen C Lazarus - University of California, San FranciscoSurya P Bhatt - University of Alabama at BirminghamDavid M MacDonald - University of MinnesotaTakudzwa Mkorombindo - University of Alabama at BirminghamKen M Kunisaki - University of MinnesotaSpyridon Fortis - University of Iowa Hospitals and ClinicsDavid Kaminsky - University of VermontMark T Dransfield - University of Alabama at Birmingham
- Resource Type
- Journal article
- Publication Details
- Annals of the American Thoracic Society, Vol.19(10), pp.1642-1649
- DOI
- 10.1513/AnnalsATS.202109-1042OC
- PMID
- 35363600
- PMCID
- PMC9528740
- ISSN
- 1546-3222
- eISSN
- 2325-6621
- Grant note
- K23 HL153672 / NHLBI NIH HHS
- Language
- English
- Date published
- 10/2022
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984359811202771
Metrics
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