Beta-blockers doubled risk of hospitalization from COPD exacerbations (BLOCK-COPD)

Beta-blockers have generally been considered safe and beneficial for patients with COPD, but a new randomized trial calls that assumption into doubt. The use of oral beta blockers without a cardiac indication appeared to double the risk of hospitalization for people experiencing a COPD exacerbation.

Authors randomized 532 patients with moderate or severe COPD with an exacerbation within the past year to receive either extended release metoprolol or placebo. Patients were not already taking beta blockers and had not had myocardial infarctions or other cardiac indications for beta blocker use. The trial was called BLOCK-COPD and was published in the New England Journal of Medicine.

Over about a year of follow-up, patients receiving metoprolol or placebo had about the same frequency of COPD exacerbations. However, patients taking metoprolol had almost twice the rate of hospitalization. Serious COPD exacerbations occurred at rates of 0.43 and 0.19 per person-year, respectively, in the beta-blocker and placebo groups (P=0.02). BLOCK COPD was terminated early out of apparent futility and concern for safety.

Deaths among patients taking metoprolol outnumbered those in the placebo group (11 vs 5, not statistically significant). There were no significant differences in lung function, exercise tolerance or dyspnea symptoms.

People with COPD frequently have comorbid cardiovascular disease such as congestive heart failure, which increases the risk for complex multifactorial respiratory decompensations, which may often be diagnosed as COPD exacerbations.

Beta blockers are recommended for most patients with systolic heart failure and/or a history of myocardial infarction; those patients were excluded from BLOCK COPD.

The study’s findings were surprising, as observational studies have suggested that beta blockers reduce the risk of death and respiratory decompensations in people with COPD.

A possible mechanism was inhibition of beta-adrenergic receptor-mediated bronchodilation -- in other words, beta blockade could worsen bronchospasm and reduce efficacy of albuterol or other beta-agonists, making COPD exacerbations more frequent, or worse. This has long been an anecdotal concern, until now without the support of high quality randomized trial data. BLOCK-COPD was not designed to explain why the effect was observed.

An editorialist concluded that

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, with the caveat that the risk-benefit ratio should be considered carefully in patients with very severe COPD at high risk for severe exacerbations."

Source: NEJM