Beta-Blockers May Reduce Mortality and Exacerbations in COPD
Rutten FH, Zuithoff NP, Hak E, Grobbee DE, Hoes AW
Arch Intern Med. 2010;170:880-887
For many years, beta-blockers have been avoided in patients with chronic obstructive pulmonary disease (COPD) because of the theoretical, and sometimes real, risk of increasing airway obstruction. But in COPD, coronary artery disease and heart failure are common comorbidities for which a beta-blocker may be appropriate.
To determine the safety of beta-blocker use in COPD, Rutten and colleagues conducted a retrospective review of the electronic pharmacy records of a primary care network in The Netherlands. The study included all patients over age 45 years with the diagnosis of COPD, emphysema, or chronic bronchitis, and recorded all-cause mortality and acute exacerbations of COPD as coprimary outcomes. The Cox proportional hazards test was used to analyze the risk of each coprimary outcome associated with the use of any beta-blocker, as well as separately for selective and nonselective beta-blockers.
Between 1995 and 2005, a total of 2230 patients were followed for a mean of 7.2 years during which 686 died. Of patients who took a beta-blocker, 27.2% died; and of patients who did not take beta-blockers, 32.3% died (P < .02). In subgroup analyses, the benefit of a cardioselective blocker was almost twice that of a nonselective blocker. One or more acute exacerbations occurred in 1055 patients (42.7% of patients who took a beta-blocker and 49.3% of those who did not take a beta blocker, P < .005.) The investigators concluded that "treatment with beta-blockers may reduce the risk of exacerbations and improve survival in patients with COPD."
It has been accepted dogma for many years that beta-blockers should be avoided in patients with reversible airway obstruction, including COPD, because these agents can increase airway obstruction by blocking the endogenous and exogenous bronchodilator effect of beta-agonism. Cardioselective beta-blockers were developed, in part, to avoid this effect, and evidence suggests that these agents are indeed well-tolerated by patients with either asthma or COPD. However, the idea that cardioselective, and even noncardioselective blockers, can improve clinically-based outcomes in COPD is new. It is well known that these agents improve important outcomes in coronary artery disease, but they tend nevertheless to be avoided when patients have concomitant COPD or asthma.This caution is unwarranted in COPD. Furthermore, it now appears that long-term use of a beta-blocker may actually reduce the risk of death or acute exacerbations in COPD. If correct, the mechanism of this effect is obscure.
The study has limitations, a major one being that the study was retrospective with all the well-known confounding factors that cloud such studies: uncertainty about the precision of the clinical diagnosis, inability to correct for disease severity, and so forth. Possibly too, the survival effect could have been the result of the effect of beta-blockers on patients with cardiovascular disease. Those uncertainties could be addressed by a well-designed prospective study, but unless a government agency decides to fund it, the likelihood is remote that such a study will ever be performed.
Abstract
Beta-Blockers May Reduce Mortality and Risk of Exacerbations in Patients With Chronic Obstructive Pulmonary Disease
Rutten FH, Zuithoff NP, Hak E, Grobbee DE, Hoes AW
Arch Intern Med. 2010;170:880-887
Study Summary
For many years, beta-blockers have been avoided in patients with chronic obstructive pulmonary disease (COPD) because of the theoretical, and sometimes real, risk of increasing airway obstruction. But in COPD, coronary artery disease and heart failure are common comorbidities for which a beta-blocker may be appropriate.
To determine the safety of beta-blocker use in COPD, Rutten and colleagues conducted a retrospective review of the electronic pharmacy records of a primary care network in The Netherlands. The study included all patients over age 45 years with the diagnosis of COPD, emphysema, or chronic bronchitis, and recorded all-cause mortality and acute exacerbations of COPD as coprimary outcomes. The Cox proportional hazards test was used to analyze the risk of each coprimary outcome associated with the use of any beta-blocker, as well as separately for selective and nonselective beta-blockers.
Between 1995 and 2005, a total of 2230 patients were followed for a mean of 7.2 years during which 686 died. Of patients who took a beta-blocker, 27.2% died; and of patients who did not take beta-blockers, 32.3% died (P < .02). In subgroup analyses, the benefit of a cardioselective blocker was almost twice that of a nonselective blocker. One or more acute exacerbations occurred in 1055 patients (42.7% of patients who took a beta-blocker and 49.3% of those who did not take a beta blocker, P < .005.) The investigators concluded that "treatment with beta-blockers may reduce the risk of exacerbations and improve survival in patients with COPD."
Viewpoint
It has been accepted dogma for many years that beta-blockers should be avoided in patients with reversible airway obstruction, including COPD, because these agents can increase airway obstruction by blocking the endogenous and exogenous bronchodilator effect of beta-agonism. Cardioselective beta-blockers were developed, in part, to avoid this effect, and evidence suggests that these agents are indeed well-tolerated by patients with either asthma or COPD. However, the idea that cardioselective, and even noncardioselective blockers, can improve clinically-based outcomes in COPD is new. It is well known that these agents improve important outcomes in coronary artery disease, but they tend nevertheless to be avoided when patients have concomitant COPD or asthma.This caution is unwarranted in COPD. Furthermore, it now appears that long-term use of a beta-blocker may actually reduce the risk of death or acute exacerbations in COPD. If correct, the mechanism of this effect is obscure.
The study has limitations, a major one being that the study was retrospective with all the well-known confounding factors that cloud such studies: uncertainty about the precision of the clinical diagnosis, inability to correct for disease severity, and so forth. Possibly too, the survival effect could have been the result of the effect of beta-blockers on patients with cardiovascular disease. Those uncertainties could be addressed by a well-designed prospective study, but unless a government agency decides to fund it, the likelihood is remote that such a study will ever be performed.
Abstract
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