Association between P-pulmonale and respiratory morbidity in COPD: a secondary analysis of the BLOCK-COPD trial

R. Chad Wade, Takudzwa Mkorombindo, Sharon X. Ling, Erika S. Helgeson, David M. MacDonald, Krystle Pew, Helen Voelker, Vera Bittner, Ken M. Kunisaki, Matthew R. Lammi, Mark T. Dransfield

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number434
JournalBMC Pulmonary Medicine
Volume23
Issue number1
DOIs
StatePublished - Dec 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

Keywords

  • Acute exacerbation
  • COPD
  • Electrocardiography
  • Pulmonary hypertension

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