Birmingham, AL—Multiple observational studies have suggested that beta-blockers benefit patients with moderate or severe chronic obstructive pulmonary disease (COPD) and coexisting cardiovascular disease, with outcomes similar to those observed in patients without COPD.

A new article in the New England Journal of Medicine also points out that several nonrandomized observational studies involving COPD patients have found indications that beta-blockers reduce the risk of exacerbations and death, regardless of the presence of cardiac disease, although that has not been confirmed in clinical trials. It is well established, however, that beta-blockers reduce mortality in patients who have had myocardial infarction and in those with heart failure, according to the report.

Yet according to the BLOCK COPD Trial Group led by University of Alabama at Birmingham researchers, COPD patients 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.”

To better inform the debate, the study team conducted a prospective, randomized trial, assigning COPD patients between the ages of 40 and 85 years to receive either a beta-blocker (extended-release metoprolol) or placebo.

The 532 participants all had a clinical history of COPD, along with moderate airflow limitation and an increased risk of exacerbations, which was determined by a history of exacerbations during the previous year or the prescribed use of supplemental oxygen. The mean (±SD) age of the patients was 65.0±7.8 years, while the mean forced expiratory volume in 1 second (FEV1) was 41.1±16.3% of the predicted value. Excluded were patients who were already taking a beta-blocker or who had an established indication for the use of such drugs.

Defined as the primary end point was the time until the first exacerbation of COPD during the treatment period, which, depending on the adjusted dose of metoprolol, ranged from 336 to 350 days. The authors report that the trial was stopped early because of futility with respect to the primary end point and safety concerns.

Results indicated 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 [HR] for metoprolol vs. placebo, 1.05; 95% CI, 0.84-1.32; P =. 66). Metoprolol was found, however, to be associated with a higher risk of exacerbation leading to hospitalization (HR, 1.91; 95% CI, 1.29-2.83).

With 11 deaths in the metoprolol group and five in the placebo group, the study said that the side-effect frequency that could be related to metoprolol was similar in the two groups, as was the overall rate of nonrespiratory serious adverse events.

Despite long-stated concerns, researchers emphasize that they did not find evidence of a difference in the risk of COPD exacerbation between the metoprolol group and the placebo group, although hospitalization appeared to be more likely after exacerbation in those using metoprolol.

In addition, they write, “These results differ from previously reported findings from observational studies suggesting that beta-blockers reduce the risks of exacerbation and death from any cause in patients with COPD. Although observational studies have suggested that the benefits of beta-blockers in patients with recent myocardial infarction and heart failure extend to those with COPD, this hypothesis has not been prospectively confirmed, and randomized trials to determine the overall risk-benefit ratio in such patients may be needed.”

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