Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published December 11, 2019


Did the use of metoprolol reduce the risk of COPD exacerbation, as compared to placebo, in the trial by Dransfield et al.?

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. Dransfield et al. investigated the effect of the beta-blocker metoprolol, as compared with placebo, on the risk of COPD exacerbations among patients who were at high risk for such events. Read the Original Article here.

Clinical Pearls

Q: What have observational studies suggested regarding the use of beta-blockers in patients with COPD?

A: Observational studies suggest that beta-blockers may reduce the risk of exacerbation and death in patients with moderate or severe COPD, but these findings have not been confirmed in randomized trials.

Q: Are patients with COPD often treated with beta-blockers?

A: It is well established that beta-blockers reduce mortality in patients after myocardial infarction and in those with heart failure. Patients with COPD are often not treated with this class of medications, even when they have an evidence-based indication for the use of such drugs, because of concern about possible adverse effects on lung function.

Morning Report Questions

Q: Did the use of metoprolol reduce the risk of COPD exacerbation, as compared to placebo, in the trial by Dransfield et al.?

A: The trial was stopped early because of futility with respect to the primary end point and safety concerns. The authors did not find evidence of a difference in the risk of COPD exacerbation between the metoprolol group and the placebo group, although the use of metoprolol was associated with a higher risk of an exacerbation leading to hospitalization. There was no significant between-group difference in the median time until the first exacerbation, which was 202 days (95% confidence interval [CI], 162 to 282) in the metoprolol group and 222 days (95% CI, 189 to 295) in the placebo group. The unadjusted hazard ratio for the comparison between metoprolol and placebo was 1.05 (95% CI, 0.84 to 1.32; P=0.66), which was similar after adjustment (hazard ratio, 1.12; 95% CI, 0.88 to 1.42). For the time until the first exacerbation of moderate severity or greater, the unadjusted hazard ratio was 1.47 (95% CI, 1.06 to 2.04) and the adjusted hazard ratio was 1.46 (95% CI, 1.03 to 2.06). For severe or very severe exacerbations, the unadjusted and adjusted hazard ratios were 1.91 (95% CI, 1.29 to 2.83) and 2.08 (95% CI, 1.37 to 3.14), respectively. Metoprolol was associated with worsening of dyspnea and of the overall burden of COPD symptoms, as measured by the shortness-of-breath questionnaire and the COPD Assessment Test.

Q: What were some of the limitations of the trial by Dransfield et al.?

A: The trial population had moderate or severe COPD with a high prevalence of supplemental oxygen use and previous hospitalization for COPD. Thus, the authors do not know whether their results would apply to patients with mild airflow obstruction or a lower exacerbation risk. In part because the trial was stopped early, the authors had limited power to detect differences in the risk of severe exacerbation between subgroups and could not identify specific factors that predisposed patients to adverse outcomes when treated with metoprolol. The trial did not enroll patients who had a proven indication for the use of a beta-blocker or who were already taking the drugs, so the results do not inform the risk of COPD exacerbations with metoprolol in such patients.

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