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Chronic obstructive pulmonary disease (COPD) is currently recognised as an inflammatory disease associated with significant extrapulmonary effects and important comorbidities, including ischaemic heart disease and heart failure.1 Despite ample evidence of the benefits of β-blockers in hypertension, ischaemic heart disease and congestive heart failure, use of β-blockers is >50% lower in heart failure patients with than without COPD,2 probably because of concern regarding the possibility of bronchospasm provoked by β-blockers in patients with underlying obstructive lung disease, despite evidence to the contrary.3 In view of the compelling evidence demonstrating beneficial effects of β-blockers in cardiovascular disease (CVD), including improved survival, failure to prescribe these agents in patients with COPD and concomitant CVD denies these benefits to such patients. A recent observational cohort study of patients with COPD demonstrated a favourable effect of β-blockers in reducing all-cause mortality, as well as exacerbations of COPD, irrespective of the presence or absence of overt CVD, suggesting ‘dual cardiopulmonary protective properties’ of β-blockers.4 The report by Short and colleagues seeks to extend these findings by investigating the effect of β-blockers added to specific treatment regimens for COPD across the spectrum of disease severity.
Short and colleagues performed a 9-year retrospective cohort study using a Scottish respiratory disease-specific database comprising nearly 6000 COPD patients >50 years of age to examine the effect of treatment with β-blockers (vs no β-blockers) when added to existing therapy for COPD of varying stages of severity defined by Global Initiative for Chronic Obstructive Lung Disease guidelines.1 The authors implemented Cox regression models to derive HRs for the association of β-blocker use with all-cause mortality, adjusting for relevant covariates including age, gender, smoking, lung function (marker of COPD severity), cardiac disease history and use of various cardiac drugs. Subgroup analyses were performed based on particular COPD severity-related treatment regimens. Outcomes included lung function, all-cause mortality, cardiac or respiratory mortality and COPD exacerbations defined by emergency oral steroid prescriptions and hospitalisations for COPD.
Results failed to reveal any deleterious effect of β-blockers on lung function when added to any of the various treatment regimens for COPD and also demonstrated a significant reduction in all-cause mortality (HR 0.78) and death because of myocardial infarction or COPD within most of the COPD treatment categories. Benefits of β-blockers were also observed for reducing exacerbations and hospitalisations for COPD.
The limitations of the study include those common to most retrospective observational cohort studies, including the inability to completely adjust for all possible confounders and, in particular, the potential for confounding by indication, in this case, the indication for prescribing β-blockers. Although the authors took into account overt CVD, they were unable to adjust for undiagnosed CVD. It is also possible that congestive heart failure, for example, may have accounted for some of the so-called exacerbations and hospitalisations attributed to COPD.
Together with previously published results,4 the current findings have important clinical implications. Physicians need to carefully assess their patients with COPD for clinical evidence of cardiovascular comorbidity to which they are already predisposed by their underlying COPD and their history of smoking. It is crucial to correct the misperception that cardioselective β-blockers are harmful in COPD or that they compromise the benefits of β-agonist therapy. Particularly interesting about the findings from this and an earlier study4 are the apparent benefits of β-blockers in COPD patients independent of coexisting CVD, particularly, the reductions in COPD exacerbations and hospitalisations for COPD. The mechanism of this apparent lung-specific benefit is unclear. Although the authors suggest that upregulation of β-receptors may account for the benefit by improving bronchodilator responsiveness to β-agonists, this potential mechanism remains speculative. Additional studies are warranted to investigate the mechanism of the apparent beneficial effects of β-blockers on COPD-specific outcomes. Randomised controlled trials would also be useful to validate the findings of this retrospective observational study and extend the results to other outcomes, including health-related quality of life and lung function decline.
Competing interests None.
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