麻豆传媒

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NEW ORLEANS -- Treatment with a beta blocker failed to increase the time to exacerbation and was associated with more hospitalizations in patients with COPD without established cardiovascular indications for beta-blocker use in a study reported here.

Among 532 patients with moderate to severe COPD without a history of myocardial infarction of other indication for beta blocker use, treatment with extended-release metoprolol did not lengthen the time to exacerbation compared to placebo, reported Mark T. Dransfield, MD, of the University of Alabama Birmingham Lung Health Center.

Results from the prospective, randomized -- presented at the and published simultaneously in the -- also showed metoprolol treatment was associated with almost double the risk of experiencing an exacerbation leading to hospitalization (hazard ratio 1.91, 95% CI 1.29-2.83), although use of the drug did not appear to worsen lung function.

The trial was terminated early last March.

"The [safety monitoring] committee recommended that the trial be stopped for two reasons: number one was futility for the primary endpoint and secondly for safety concerns," Dransfield said.

He noted that patients with COPD have roughly five times higher risk for cardiovascular events than the general population of similar rate, and that cardiovascular disease increases the risk for COPD exacerbations.

Beta-blockers reduce mortality in people with established cardiovascular disease, but the question of whether COPD patients without established CVD should get them has been the subject of much speculation. Findings from several observational studies suggested that beta-blockers do reduce mortality risk and respiratory events in these patients, but randomized trials were absent.

In an interview with 麻豆传媒, Dransfield said the trial findings from BLOCK COPD confirm that metoprolol is not beneficial, and may be harmful, in patients who do not have indications to be on a beta-blocker.

"If patients with COPD do not have these indications, they should not be on the drug," he said.

Commenting on the study findings at Dransfield's presentation, Gerard J. Criner, MD, of the Lewis Katz School of Medicine at Temple University, Philadelphia, noted that while beta blockers are still indicated in patients with heart failure and ischemic heart disease, their use in other groups, including COPD patients without CVD, should be reevaluated.

"I think, overall, it's time to revisit the role of beta-blockers to decrease cardiac risk in patients who are at risk for COPD , especially since there are newer available cardiac agents and reperfusion therapies that are now the mainstay of treatment for these patients," he said.

Study details

All patients included in the trial had experienced COPD exacerbations within the previous year. Patients were excluded if they were already taking a beta blocker or if they had established indications for use of the drug.

Mean patient age was 65 and just over half were men. Two-thirds of those assigned to metoprolol and three-quarters of the placebo group were white. About half were current or former smokers. Mean value at enrollment was about 41% of predicted (after bronchodilation) in both treatment groups. In addition to receiving metoprolol or placebo, patients continued on their previous medications, mostly some combination of inhaled steroids, long-acting beta agonists, and/or long-acting muscarinic antagonists.

The primary study endpoint was time to first exacerbation during treatment. Median values for this measure were 202 and 222 days for patients in the metoprolol and placebo groups, respectively, though the difference did not reach statistical significance.

Side effects were also similar in the two groups, although deaths with metoprolol outnumbered those in the placebo group, at 11 to five.

No significant between-group differences were identified in change from baseline in FEV₁, 6-minute walk distance, and score on the St. George's Respiratory Questionnaire.

Rates of hospitalization for any cause were 0.66 per person-year in the metoprolol group and 0.42 per person-year in the placebo group (P not reported) and the rate of overall nonfatal serious adverse events was 0.65 per person-year in the beta-blocker group and 0.43 in the placebo group (P=0.07). Non-fatal serious COPD exacerbations occurred at a rate of 0.43 and 0.19 per person-year, respectively, in the beta-blocker and placebo groups (P=0.02).

In an in NEJM, William MacNee, MD, of the University of Edinburgh Medical School, stressed that clinicians should not be reluctant to prescribe beta-blockers to COPD patients with indications for their use, based on the findings.

He noted that there is little evidence that beta-blockers are currently being prescribed in COPD patients without therapeutic indications for their use.

"On the contrary, there is good evidence that physicians are still reluctant to prescribe beta-blockers even in patients with COPD who have proven cardiac indications," MacNee wrote. "The results of this trial should not deter the use of beta-blockers in patients with COPD who have cardiovascular indications, with the caveat that the risk-benefit ratio should be considered carefully in patients with very severe COPD at high risk for severe exacerbations."