EvidenceAlerts

Dransfield MT, Voelker H, Bhatt SP, et al. Metoprolol for the Prevention of Acute Exacerbations of COPD. N Engl J Med. 2019 Oct 20. doi: 10.1056/NEJMoa1908142. (Original study)
Abstract

BACKGROUND: Observational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease (COPD), but these findings have not been confirmed in randomized trials.

METHODS: In this prospective, randomized trial, we assigned patients between the ages of 40 and 85 years who had COPD to receive either a beta-blocker (extended-release metoprolol) or placebo. All the patients had a clinical history of COPD, along with moderate airflow limitation and an increased risk of exacerbations, as evidenced by a history of exacerbations during the previous year or the prescribed use of supplemental oxygen. We excluded patients who were already taking a beta-blocker or who had an established indication for the use of such drugs. The primary end point was the time until the first exacerbation of COPD during the treatment period, which ranged from 336 to 350 days, depending on the adjusted dose of metoprolol.

RESULTS: A total of 532 patients underwent randomization. The mean (±SD) age of the patients was 65.0±7.8 years; the mean forced expiratory volume in 1 second (FEV1) was 41.1±16.3% of the predicted value. The trial was stopped early because of futility with respect to the primary end point and safety concerns. There was no significant between-group difference in the median time until the first exacerbation, which was 202 days in the metoprolol group and 222 days in the placebo group (hazard ratio for metoprolol vs. placebo, 1.05; 95% confidence interval [CI], 0.84 to 1.32; P = 0.66). Metoprolol was associated with a higher risk of exacerbation leading to hospitalization (hazard ratio, 1.91; 95% CI, 1.29 to 2.83). The frequency of side effects that were possibly related to metoprolol was similar in the two groups, as was the overall rate of nonrespiratory serious adverse events. During the treatment period, there were 11 deaths in the metoprolol group and 5 in the placebo group.

CONCLUSIONS: Among patients with moderate or severe COPD who did not have an established indication for beta-blocker use, the time until the first COPD exacerbation was similar in the metoprolol group and the placebo group. Hospitalization for exacerbation was more common among the patients treated with metoprolol. (Funded by the Department of Defense; BLOCK COPD ClinicalTrials.gov number, NCT02587351.).


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Ratings
Discipline Area Score
Respirology/Pulmonology 6 / 7
Internal Medicine 6 / 7
Family Medicine (FM)/General Practice (GP) 5 / 7
General Internal Medicine-Primary Care(US) 5 / 7
Comments from MORE raters

Family Medicine (FM)/General Practice (GP) rater

I was taught that beta-blockers should be avoided in patients with obstructive lung disease, including COPD. This study supports that assessment. There was no benefit in those randomized to metoprolol. More patients were harmed in the metoprolol group, primarily due to more severe exacerbations. What gives me particular pause is that the metoprolol group had an absolute increase in risk for death. This was not statistically significant, so maybe it is not a real effect, but the study was small. For the outcome of mortality, the number needed to harm from treatment with metoprolol calculates to be 45. Again, not statistically significant, but given that there was no benefit with treatment with metoprolol, this trend makes me more inclined to avoid beta-blockers in COPD patients, unless there is a compelling reason to prescribe them.

General Internal Medicine-Primary Care(US) rater

I find the basic underpinnings of this article to be faulty.

General Internal Medicine-Primary Care(US) rater

Many primary care providers believe that beta-blockers can cause worsening pulmonary function, and may not be aware that beta-blockers could possibly be useful in COPD. However, this study confirms that beta-blockers do not help, and this is consistent with current practice. So, although interesting, this may not change practice.

Internal Medicine rater

Severe exacerbation increase was interesting but of borderline statistical significance as a secondary endpoint. Most of us weren't using metoprolol for no indication in people with severe COPD anyway.

Respirology/Pulmonology rater

Prospective randomized trial demonstrates no indication for use of a selective beta-blocker to prevent exacerbations of lung disease in patients with COPD. Not a surprising result, but important that the hypothesis was tested.

Respirology/Pulmonology rater

This RCT finds that metoprolol did not reduce the risk for COPD exacerbations overall, and, in fact, increased the risk for severe exacerbations. The interpretation of the latter finding is a bit puzzling, but it is noteworthy that the metoprolol group was less likely to receive a LABA, and this was not adjusted for in the analysis. Metoprolol also appeared to cause a bit more dyspnea. These findings rule out a role for metoprolol as a treatment to prevent COPD exacerbations, despite promising results from observational studies. However, they do not challenge the safety of using metoprolol for cardiovascular indications in COPD patients because these patients were excluded from the study.

Respirology/Pulmonology rater

Important study that brings into question the use of beta-blockers in COPD. The study was performed in a group with moderately-severe-to-severe COPD and may or may not be representative of mild-to-moderate COPD; however, it raises a caution to primary care physicians and pulmonologists.
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