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β-blockers as Cardiopulmonary Agents: The Benefits May Not Be Limited to CVD
Abstract & Commentary
By Rahul Gupta, MD, MPH, FACP, Clinical Assistant Professor, West Virginia University School of Medicine, Charleston, WV. Dr. Gupta reports no financial relationship to this field of study.
Synopsis: In a large, well-designed observational study of patients with COPD, treatment with β-blockers during a mean follow-up period of 7.2 years was found not only to reduce the risk of exacerbations, but also to improve survival.
Source: Rutten FH, et al. β-blockers may reduce mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease. Arch Intern Med 2010;170:880-887.
Chronic obstructive pulmonary disease (COPD) is a disease of epidemic proportions worldwide. In the United States, it causes more than 120,000 deaths each year, and is currently the fourth leading cause of mortality. Additionally, due to the chronic nature of the disease and frequent exacerbations in individual patients, there is resultant higher resource utilization compared with several other chronic illnesses. The natural history and prognosis as well as the etiology of acute exacerbations in patients with COPD are incompletely understood at this time. Therefore, while a number of factors such as infections and exposure to environmental pollutants may play a role in acute exacerbations of the disease, up to one-third of cases may not have a clear etiology.1 Researchers believe some of these unknowns may be related to other medical conditions such as myocardial ischemia, heart failure, and pulmonary embolism.1,2 Currently, only a few agents used in management of COPD have been proven to prolong survival (e.g., oxygen therapy). Furthermore, most clinicians tend to restrict the use of β-blockers in the management plan of COPD patients, sometimes including those with cardiovascular comorbidities, which may deprive these patients of the beneficial cardiovascular effects from these agents and may also result in some of the so-called COPD exacerbations.
Rutten at al conducted an observational cohort study using electronic data from 23 general practices in the Netherlands to evaluate the long-term effect of β-blocker use on survival and exacerbations in patients with COPD. The study included 2230 patients with mean age of 64.8 years followed for a mean of 7.2 years. Approximately 45% of the patients with COPD had cardiovascular comorbidities and two-thirds had cardiovascular disease, hypertension, or diabetes. Their results demonstrated that treatment with β-blockers may reduce the risk of COPD exacerbations (crude and adjusted hazard ratios for exacerbations were 0.73 [95% CI, 0.63-0.83] and 0.71 [95% CI, 0.60-0.83], respectively) and improve survival (crude and adjusted hazard ratios for mortality were 0.70 [95% CI, 0.59-0.84] and 0.68 [95% CI, 0.56-0.83], respectively) in patients with a COPD diagnosis. A subgroup analysis revealed that patients with COPD but without overt cardiovascular disease had similar results. Cardioselective and nonselective β-blockers did not substantially differ in their effects on COPD exacerbations. However, cardioselective β-blockers had larger beneficial effects on mortality than nonselective ones. In their comments, the authors note that reduction in risk of exacerbation of COPD by β-blockers cannot easily be explained by beneficial cardiovascular effects alone.
For decades, β-blockers were believed to worsen heart failure due to their negative inotropic effects. However, a paradigm shift occurred when clinical trials provided evidence that β-blockers block the progressive negative impact of neurohormones (such as norepinephrine) on the failing heart and thus result in significantly positive clinical impact in the failing heart's pathophysiology. β-blockers have since become the standard of treatment as further research demonstrated that they can reduce the total mortality in patients with heart failure by 30%-40%.
Similar to the case of heart failure management, it is now emerging that in patients with COPD, several treatments used in comorbid diseases may have beneficial effects. In the past, observational studies have suggested that COPD patients treated with statins, angiotensin-converting enzymes, angiotensin receptor blockers, and β-blockers may have improved survival and reduced hospitalization from COPD exacerbations.3,4 However, the present research by Rutten et al is the first observational study to demonstrate that long-term treatment with β-blockers may improve survival and reduce the risk of an exacerbation in patients with COPD.
There may be several reasons for this including the beneficial cardiovascular effects from β-blockers, such as lowering of heart rate, or improvement in heart failure or ischemic heart disease. There may also be additional, yet unproven pulmonary benefits.
But then we must not become too optimistic too soon. Observational studies such as this one by Rutten et al are subject to several limitations and therefore well-designed prospective, randomized controlled trials must be conducted before advocating a paradigm shift. Nevertheless, the important information from this study may be the fact that we may not need fear β-blockers as much as we currently do when developing a management plan for patients with COPD. Perhaps, we should consider widening the spectrum of patients with COPD in whom we use this group of drugs.
1. Sapey E, Stockley RA. COPD exacerbations. Thorax 2006;61:250-258.
2. Barnes PJ. Chronic obstructive pulmonary disease. N Engl J Med 2000;343:269-280.
3. Barnes PJ, Celli BR. Systemic manifestations and comorbidities of COPD. Eur Respir J 2009;33:1165-1185.
4. Mancini GB, et al. Reduction of morbidity and mortal-ity by statins, angiotensin-converting enzyme inhibi-tors, and angiotensin receptor blockers in patients with chronic obstructive pulmonary disease. J Am Coll Cardiol 2006;47:2554-2560.