Beta blockers should still be used in patients with COPD and cardiovascular disease despite a trial showing they do not reduce exacerbations in patients without cardiovascular indications, researchers say.
Published in the NEJM, findings from the BLOCK COPD trial showed that metoprolol had no effect on the primary outcome of time until the first COPD exacerbation in patients with moderate airflow limitation and an increased risk of exacerbations.
The trial was stopped early due to likely futility and because patients assigned to metoprolol had a greater risk of severe and very severe exacerbations.
The US multicentre study involving 532 patients was designed as a prospective trial to confirm results from numerous observational studies that suggested beta blockers could may reduce the risk of exacerbations and death in patients with moderate or severe COPD.
Patients recruited into the study were aged 40-85 (mean 65 years) and had a mean FEV1 of 41.1% of the predicted value. Patients were deemed at high risk of exacerbation because they had a history of exacerbations during the previous year or the prescribed use of supplemental oxygen.
The treatment period with metoprolol ranged from 336 to 350 days but the trial was stopped early when there was no significant between-group difference in the median time until the first exacerbation (202 days in the metoprolol group vs 222 days for placebo).
Metoprolol was associated with a higher risk of exacerbation leading to hospitalisation (hazard ratio, 1.91) and very severe exacerbations (HR 2.08).
However there was no worsening in lung function with beta blocker use, and no evidence of between-group differences in the 6-minute walk distance or in patients’ reports of possible beta-blocker side effects.
During the treatment period, there were 11 deaths in the metoprolol group and five in the placebo group.
The investigators noted that their findings contrasted with those of a meta-analysis of 15 observational studies, in which beta blocker use was associated with a lower risk of death from any cause (relative risk, 0.72) or from COPD exacerbation (relative risk, 0.63).
This was likely due to non-prospective observational studies having high proportions of patients with in patients with cardiovascular indications such as heart failure and recent myocardial infraction, the authors suggested.
The BLOCK COPD study showed that any such benefit in preventing exacerbations did not extend to all patients with COPD, they concluded
However in a linked commentary Dr William MacNee of the University of Edinburgh Medical School, said beta blockers are not recommended for this indication in COPD generally, and physicians are still reluctant to prescribe beta-blockers even in patients with COPD who have proven cardiac indications.
“The results of this trial should not deter the use of beta-blockers in patients with COPD who have cardiovascular indications,” he wrote, “with the caveat that the risk–benefit ratio should be considered carefully in patients with very severe COPD at high risk for severe exacerbation.”