Author:
Wade R. Chad,Mkorombindo Takudzwa,Ling Sharon X.,Helgeson Erika. S.,MacDonald David M.,Pew Krystle,Voelker Helen,Bittner Vera,Kunisaki Ken M.,Lammi Matthew R.,Dransfield Mark. T.
Abstract
Abstract
Rationale
Pulmonary hypertension (PH) in COPD confers increased risk of exacerbations (ECOPD). Electrocardiogram (ECG) indicators of PH are prognostic both in PH and COPD. In the Beta-Blockers for the Prevention of Acute Exacerbations of COPD (BLOCK-COPD) trial, metoprolol increased risk of severe ECOPD through unclear mechanisms.
Objective
We evaluated whether an ECG indicator of PH, P-pulmonale, would be associated with ECOPD and whether participants with P-pulmonale randomized to metoprolol were at higher risk of ECOPD and worsened respiratory symptoms given the potential detrimental effects of beta-blockers in PH.
Methods
ECGs of 501 participants were analyzed for P-pulmonale (P wave enlargement in lead II). Cox proportional hazards models evaluated for associations between P-pulmonale and time to ECOPD (all and severe) for all participants and by treatment assignment (metoprolol vs. placebo). Linear mixed-effects models evaluated the association between treatment assignment and P-pulmonale on change in symptom scores (measured by CAT and SOBQ).
Results
We identified no association between P-pulmonale and risk of any ECOPD or severe ECOPD. However, in individuals with P-pulmonale, metoprolol was associated with increased risk for ECOPD (aHR 2.92, 95% CI: 1.45–5.85). There was no association between metoprolol and ECOPD in individuals without P-pulmonale (aHR 1.01, 95% CI: 0.77–1.31). Individuals with P-pulmonale assigned to metoprolol experienced worsening symptoms (mean increase of 3.95, 95% CI: 1.32–6.58) whereas those assigned to placebo experienced a mean improvement in CAT score of -2.45 (95% CI: -0.30- -4.61).
Conclusions
In individuals with P-pulmonale, metoprolol was associated with increased exacerbation risk and worsened symptoms. These findings may explain the findings observed in BLOCK-COPD.
Funder
U.S. Department of Defense
Publisher
Springer Science and Business Media LLC
Subject
Pulmonary and Respiratory Medicine
Reference37 articles.
1. Anees Ur R, Ahmad Hassali MA, Muhammad SA, Shah S, Abbas S, Hyder Ali IAB, Salman A. The economic burden of Chronic Obstructive Pulmonary Disease (COPD) in the USA, Europe, and Asia: results from a systematic review of the literature. Expert Rev Pharmacoecon Outcomes Res. 2020;20:661–72.
2. Miller JD, Foster T, Boulanger L, Chace M, Russell MW, Marton JP, Menzin J. Direct costs of COPD in the US: an analysis of Medical Expenditure Panel Survey (MEPS) data. COPD: J Chronic Obstr Pulmon Dis. 2005;2:311–8.
3. Foster TS, Miller JD, Marton JP, Caloyeras JP, Russell MW, Menzin J. Assessment of the economic burden of COPD in the US: a review and synthesis of the literature. COPD: J Chronic Obstr Pulmon Dis. 2006;3:211–8.
4. European Respiratory Society S. The Global Impact of Respiratory Disease. Forum of International Respiratory Societies [serial online] 2017. Available from: https://www.who.int/gard/publications/The_Global_Impact_of_Respiratory_Disease.pdf.
5. Divo MJ, Celli BR, Poblador-Plou B, Calderón-Larrañaga A, de-Torres JP, Gimeno-Feliu LA, Bertó J, Zulueta JJ, Casanova C, Pinto-Plata VM. Chronic Obstructive Pulmonary Disease (COPD) as a Disease of early aging: evidence from the EpiChron Cohort. PLoS One. 2018;13:e0193143.