Metoprolol not effective for reducing time to COPD exacerbation

Metoprolol did not appear to reduce time to an acute exacerbation of chronic obstructive pulmonary disease (COPD) among higher-risk patients in a recent randomized placebo-controlled trial.

In the BLOCK-COPD trial, researchers randomly assigned patients 40 to 85 years of age with COPD to receive extended-release metoprolol or placebo. All patients had moderate airflow limitation and were at increased risk for COPD exacerbation, defined as exacerbations during the previous year or prescribed use of supplemental oxygen. Patients already taking a beta-blocker or those with an established indication for a beta-blocker were excluded.

The study's primary end point was time until first COPD exacerbation during the treatment period. A COPD exacerbation was defined as increased or new onset of at least two of the following: cough, sputum production, wheezing, dyspnea, or chest tightness leading to treatment with antibiotics or systemic glucocorticoids for three or more days. The trial was stopped early because of futility and safety concerns, and results were published Oct. 20 by the New England Journal of Medicine.

Five hundred thirty-two patients at 26 centers in the U.S. were randomly assigned to receive metoprolol or placebo, 268 in the former group and 264 in the latter. Forty-six percent of patients were women, mean patient age was 65 years, and mean forced expiratory volume in 1 second was 41.1% of predicted. No significant difference was seen between groups in median time to first exacerbation (202 days in the metoprolol group vs. 222 days in the placebo group; unadjusted hazard ratio for metoprolol vs. placebo, 1.05 [95% CI, 0.84 to 1.32]; P=0.66), and those in the metoprolol group had a higher risk for an exacerbation that led to hospitalization (unadjusted hazard ratio, 1.91; 95% CI, 1.29 to 2.83). No between-group difference was noted in patient-reported adverse events that could have been related to the study drug. Eleven patients in the metoprolol group and five patients in the placebo group died during the treatment period, and of these deaths, seven and one, respectively, were attributed to COPD.

The researchers noted that patients and investigators were blinded to group assignment but could not be fully blinded to the effects of beta-blockade, such as reduced heart rate and blood pressure. In addition, their study tested only one beta-blocker and their results may not apply to patients with milder forms of COPD, among other limitations. However, they concluded that risk for COPD exacerbations was similar in higher-risk patients with moderate or severe COPD but no indication for beta-blockers.

“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,” the authors wrote.