-blockers associated with reduced all-cause mortality in COPD
2
Prognosis 31 Evidence-Based Medicine February 2012 | volume 17 | number 1 | 10.1136/ebm.2011.100118 David Geffen School of Medicine at UCLA, Department of Medicine, Los Angeles, California, USA Correspondence to: Donald P Tashkin David Geffen School of Medicine at UCLA, Department of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA; [email protected] Cohort β-blockers associated with reduced all-cause mortality in COPD Donald P Tashkin Context Chronic obstructive pulmonary disease (COPD) is cur- rently 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 dem- onstrating beneficial effects of β-blockers in cardiovas- cular 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 prop- erties’ 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. Methods Short and colleagues performed a 9-year retrospective cohort study using a Scottish respiratory disease-spe- cific 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 Commentary on: Short PM, Lipworth SI, Elder DH, et al. Effect of beta blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. BMJ 2011;342:d2549. 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. Findings Results failed to reveal any deleterious effect of β-blockers on lung function when added to any of the various treat- ment regimens for COPD and also demonstrated a signifi- cant 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 hos- pitalisations for COPD. Commentary The limitations of the study include those common to most retrospective observational cohort studies, includ- ing the inability to completely adjust for all possible con- founders 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 exacerba- tions 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 cor- rect the misperception that cardioselective β-blockers are
Transcript of -blockers associated with reduced all-cause mortality in COPD
Prognosis
31Evidence-Based Medicine February 2012 | volume 17 | number 1 |
10.1136/ebm.2011.100118
David Geffen School of Medicine at UCLA, Department of Medicine, Los Angeles, California, USA
Correspondence to:Donald P TashkinDavid Geffen School of Medicine at UCLA, Department of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA; [email protected]
Cohort
β-blockers associated with reduced all-cause mortality in COPD
Donald P Tashkin
ContextChronic obstructive pulmonary disease (COPD) is cur-rently recognised as an infl ammatory disease associated with signifi cant extrapulmonary effects and important comorbidities, including ischaemic heart disease and heart failure.1 Despite ample evidence of the benefi ts 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 dem-onstrating benefi cial effects of β-blockers in cardiovas-cular disease (CVD), including improved survival, failure to prescribe these agents in patients with COPD and concomitant CVD denies these benefi ts 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 prop-erties’ of β-blockers.4 The report by Short and colleagues seeks to extend these fi ndings by investigating the effect of β-blockers added to specifi c treatment regimens for COPD across the spectrum of disease severity.
MethodsShort and colleagues performed a 9-year retrospective cohort study using a Scottish respiratory disease-spe-cifi c 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 defi ned 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
Commentary on: Short PM, Lipworth SI, Elder DH, et al. Effect of beta blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. BMJ 2011;342:d2549.
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 defi ned by emergency oral steroid prescriptions and hospitalisations for COPD.
FindingsResults failed to reveal any deleterious effect of β-blockers on lung function when added to any of the various treat-ment regimens for COPD and also demonstrated a signifi -cant reduction in all-cause mortality (HR 0.78) and death because of myocardial infarction or COPD within most of the COPD treatment categories. Benefi ts of β-blockers were also observed for reducing exacerbations and hos-pitalisations for COPD.
CommentaryThe limitations of the study include those common to most retrospective observational cohort studies, includ-ing the inability to completely adjust for all possible con-founders 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 exacerba-tions and hospitalisations attributed to COPD.
Together with previously published results,4 the current fi ndings 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 cor-rect the misperception that cardioselective β-blockers are
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Prognosis
32 Evidence-Based Medicine February 2012 | volume 17 | number 1 |
harmful in COPD or that they compromise the benefi ts of β-agonist therapy. Particularly interesting about the fi ndings from this and an earlier study4 are the appar-ent benefi ts of β-blockers in COPD patients indepen-dent of coexisting CVD, particularly, the reductions in COPD exacerbations and hospitalisations for COPD. The mechanism of this apparent lung-specifi c benefi t is unclear. Although the authors suggest that upregulation of β-receptors may account for the benefi t by improving bronchodilator responsiveness to β-agonists, this poten-tial mechanism remains speculative. Additional studies are warranted to investigate the mechanism of the appar-ent benefi cial effects of β-blockers on COPD-specifi c out-comes. Randomised controlled trials would also be useful to validate the fi ndings 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.
References 1. Global Initiative for Chronic Obstructive Lung Disease
(GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2010. http://www.goldcopd.com (accessed June 9 2011).
2. Hawkins NM, Jhund PS, Simpson CR, et al. Primary care burden and treatment of patients with heart failure and chronic obstructive pulmonary disease in Scotland. Eur J Heart Fail 2010;12:17–24.
3. Salpeter SR, Ormiston TM, Salpeter EE, et al. Cardioselective beta-blockers for chronic obstructive pulmonary disease: a meta-analysis. Respir Med 2003;97:1094–101.
4. Rutten FH, Zuithoff NP, Hak E, et al. Beta-blockers may reduce mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease. Arch Intern Med 2010;170:880–7.
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