From Pages to Practice
The diagnosis of chronic obstructive pulmonary disease (COPD) rarely occurs in isolation, given its link to age and cigarette smoking. Indeed, in the 2020 iteration of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report, an entire chapter is dedicated to management of COPD in the context of comorbidity. Cardiovascular comorbidity is by far the most common, with a relative risk of 4.01 (95% CI, 3.6–4.4) in incidentally diagnosed COPD patients as compared to non-COPD controls.
Despite proven mortality benefits of beta-blockers in patients with heart failure and for the secondary prevention of myocardial infarction, they are under-prescribed in patients with these indications and comorbid COPD. The theoretical fear, of course, is that beta-blockade within the lung will lead to progressive bronchoconstriction and worsening of airway obstruction regardless of its salutary cardiac effects. However, observational studies have suggested that the benefits of beta-blockade in cardiovascular disease extends to patients with comorbid COPD. In fact, the observational data on exacerbation reduction was so compelling that it led to the hypothesis that beta-blockade may have a noncardiac role in the prevention of exacerbations in patients with COPD.
That hypothesis was tested in the BLOCK-COPD trial, the first randomized trial to examine the effects of beta-blockade in patients with COPD who do not have a cardiac indication for the drug. With a primary outcome of time to first exacerbation, the trial was stopped early because of futility and safety concerns with a possible association between severe exacerbations and beta-blocker use.
While these results will help physicians make more nuanced care decisions for patients with COPD, the findings do not negate the beneficial effects of beta-blockade in patients with an evidence-based cardiac indication and a co-diagnosis of COPD.
The following NEJM Journal Watch summary explains the study and results in more detail.
Allan S. Brett, MD reviewing Dransfield MT et al. N Engl J Med 2019 Oct 20
Non-cardioselective β-blockers can provoke or worsen bronchospasm in patients with chronic obstructive pulmonary disease (COPD) or asthma. In contrast, cardioselective β-blockers (e.g., metoprolol) are thought to be relatively safe for such patients. In fact, observational studies have suggested that these drugs might lower exacerbation rates and mortality in COPD patients (NEJM JW Hosp Med Aug 2010 and JAMA Intern Med 2010; 170:880). To test this possibility, U.S. researchers conducted a randomized trial that involved 532 COPD patients, most of whom had moderate or severe disease (mean forced expiratory volume in 1 second [FEV1], 41% of predicted value) and at least one exacerbation during the previous year. Patients with cardiovascular indications for β-blockers (e.g., coronary disease, heart failure) and patients with heart rates <65 beats per minute or systolic blood pressure <100 mm Hg were excluded.
Patients received extended-release metoprolol (dose, 25–100 mg daily, depending on heart rate and blood pressure) or placebo. During average follow-up of nearly 1 year, no significant difference was observed between groups in overall exacerbation rates. However, metoprolol recipients were significantly more likely to be hospitalized for COPD exacerbations (0.45 vs. 0.28 exacerbations per person-year). At routine follow-up visits, metoprolol recipients reported more dyspnea than did placebo recipients, but no differences in FEV1 were noted.
Comment: In this study, metoprolol appeared to raise risk for a severe COPD exacerbation; given that metoprolol did not worsen FEV1, the reason for this outcome is unclear. Cardioselective β-blockers remain appropriate for COPD patients who have valid cardiovascular indications for their use, but this study suggests that COPD patients without such indications should avoid these drugs.