Metoprolol in patients with P-pulmonale and chronic obstructive pulmonary disease (COPD) is associated with increased risk for COPD exacerbations (ECOPD) and worsening symptoms, according to post-hoc analysis findings published in BMC Pulmonary Medicine.
Investigators sought to determine whether P-pulmonale (P-wave enlargement, an indicator of right heart dysfunction [RHD] in pulmonary hypertension [PH]) is associated with increased risk for ECOPD, and whether ECOPD risk increased with worsening respiratory symptoms in patients with P-pulmonale treated with metoprolol.
The investigators conducted a post-hoc analysis of the BLOCK-COPD trial (ClinicalTrials.gov Identifier: NCT02587351), a multicenter, double-blind, placebo controlled, randomized, prospective trial of 532 patients (40-85 years of age) with at least moderate COPD (confirmed with spirometry). The BLOCK-COPD trial was designed to evaluate the effect of metoprolol on time-to-first exacerbation. Participants had either a prescription for supplemental home oxygen or an exacerbation history in the previous year. Patients with history of myocardial infarction within 36 months or heart failure with reduced ejection fraction less than 40% were excluded.
COPD exacerbation was defined as an increase in or a new onset of at least 2 symptoms (wheezing, sputum production, dyspnea, cough, or chest tightness leading to treatment with antibiotics or systemic glucocorticoids for at least 3 days).
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These findings suggest that metoprolol therapy may increase respiratory symptoms and exacerbation risk in COPD patients with ECG evidence of right heart dysfunction.
The current post hoc analysis included 501 patients from the BLOCK COPD trial who did not have obscured P-waves on electrocardiograms (mean [SD] age, 65.1 [7.8] years; 46.5% women; 71.3% White, 25.3% Black; mean post bronchodilator forced expiratory volume in the first second [FEV1] percent predicted, 40.6% [16.1]). Of those included in the post hoc analysis, 255 had been randomly assigned to metoprolol and 246 to placebo. P-pulmonale was present in 63 participants (metoprolol group, n=36; placebo group, n=27) and absent in 438 participants.
Significant demographic and clinical differences between the metoprolol vs placebo groups were mean FEV1 percent predicted (35.8% vs 41.4%, respectively; P =.010), and mean heart rate (90.3 vs 83.7, respectively; P <.001).
The investigators found risk for any ECOPD or severe ECOPD was not associated with P-pulmonale, although in individuals with P-pulmonale, metoprolol was associated with increased risk for ECOPD (adjusted hazard ratio [aHR], 2.92; 95% CI, 1.45-5.85). The investigators found no association between metoprolol and increased risk for ECOPD among patients without P-pulmonale (aHR, 1.01; 95% CI, 0.77-1.31).
Worsening symptoms were reported by patients with P-pulmonale treated with metoprolol (mean increase, 3.95; 95% CI, 1.32-6.58). Patients in the placebo group experienced mean COPD assessment test score improvement of -2.45 (95% CI, -0.30 to -4.61).
Post-hoc analysis limitations include electrocardiogram (ECG) changes insensitive to identifying RHD and PH (compared with echocardiography, right heart catheterization, or cardiac magnetic resonance imaging), and differences in findings between the post hoc analysis and the parent study.
“[M]etoprolol is associated with an increased risk of exacerbation and worsening COPD symptoms in individuals with P-pulmonale,” the investigators concluded. “These findings suggest that metoprolol therapy may increase respiratory symptoms and exacerbation risk in COPD patients with ECG evidence of right heart dysfunction,” the researchers added.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
