Effect of Beta Blockers in Treatment of COPD
Objective To examine the effect of β blockers in the management of chronic obstructive pulmonary disease (COPD), assessing their effect on mortality, hospital admissions, and exacerbations of COPD when added to established treatment for COPD.
Design Retrospective cohort study using a disease specific database of COPD patients (TARDIS) linked to the Scottish morbidity records of acute hospital admissions, the Tayside community pharmacy prescription records, and the General Register Office for Scotland death registry.
Setting Tayside, Scotland (2001–2010)
Population 5977 patients aged >50 years with a diagnosis of COPD.
Main outcome measures Hazard ratios for all cause mortality, emergency oral corticosteroid use, and respiratory related hospital admissions calculated through Cox proportional hazard regression after correction for influential covariates.
Results Mean follow-up was 4.35 years, mean age at diagnosis was 69.1 years, and 88% of β blockers used were cardioselective. There was a 22% overall reduction in all cause mortality with β blocker use. Furthermore, there were additive benefits of β blockers on all cause mortality at all treatment steps for COPD. Compared with controls (given only inhaled therapy with either short acting β agonists or short acting antimuscarinics), the adjusted hazard ratio for all cause mortality was 0.28 (95% CI 0.21 to 0.39) for treatment with inhaled corticosteroid, long acting β agonist, and long acting antimuscarinic plus β blocker versus 0.43 (0.38 to 0.48) without β blocker. There were similar trends showing additive benefits of β blockers in reducing oral corticosteroid use and hospital admissions due to respiratory disease. β blockers had no deleterious impact on lung function at all treatment steps when given in conjunction with either a long acting β agonist or antimuscarinic agent
Conclusions β blockers may reduce mortality and COPD exacerbations when added to established inhaled stepwise therapy for COPD, independently of overt cardiovascular disease and cardiac drugs, and without adverse effects on pulmonary function.
The presence of cardiovascular disease and chronic obstructive pulmonary disease (COPD) are intertwined because of the risk of smoking induced atherosclerosis in patients with COPD. Despite the proved benefits of β blockers in treating hypertension, ischaemic heart disease, and heart failure, many doctors are reluctant to prescribe β blockers for patients with concurrent COPD.
Historically β blockers have been avoided in asthma because of the risk of acute bronchospasm. These concerns also apply to COPD, with evidence of a reduction in forced expiratory volume in one second (FEV1), increased airway hyperresponsiveness, and inhibition of bronchodilator response to β agonists in patients receiving non-selective β blockers and high doses of cardioselective β blockers.
Despite these concerns, evidence suggests that cardioselective β blockers do not cause an increase in exacerbations, reduction in airway function, or worsening of quality of life in COPD patients. COPD is a highly heterogeneous condition, and the degree of comorbidities present seems to be independent of the degree of airway obstruction. The treatment of comorbid cardiovascular disease in COPD is especially relevant since cardiac failure has been shown to be a leading cause of death in these patients.
In this regard, the use of β blockers in patients with COPD and cardiovascular disease has been shown to reduce mortality. Whether the improved survival seen with β blockers in COPD is purely due to cardiovascular effects has been questioned. Recent evidence suggests that β blockers may improve survival and exacerbations even in COPD patients without cardiovascular disease.
Although cardioselective β blockers have been designed to target β1 adrenoceptors while avoiding β2 adrenoceptors in the lung and elsewhere, so called cardioselective β blockers (such as atenolol and bisoprolol) are only relatively selective and exert significant β2 antagonism at therapeutic doses, though to a lesser extent than non-selective β blockers such as propranolol. Thus, it might be considered counterintuitive to prescribe both β blockers and β agonists in the same patient, even when they are targeting different organs.
Current COPD management guidelines advocate a stepwise approach using long acting bronchodilators (including β agonists) and inhaled corticosteroids to reduce exacerbations and improve symptoms and lung function. With the exception of tiotropium, combination treatments involving long acting bronchodilators and inhaled corticosteroids have failed to show any significant improvement in mortality. We therefore wished to examine the use of β blockers in the management of COPD, assessing their interactions with β agonists and other COPD drug and assess whether they improve mortality, hospital admissions, and exacerbations when added to established treatment for COPD.
Abstract
Objective To examine the effect of β blockers in the management of chronic obstructive pulmonary disease (COPD), assessing their effect on mortality, hospital admissions, and exacerbations of COPD when added to established treatment for COPD.
Design Retrospective cohort study using a disease specific database of COPD patients (TARDIS) linked to the Scottish morbidity records of acute hospital admissions, the Tayside community pharmacy prescription records, and the General Register Office for Scotland death registry.
Setting Tayside, Scotland (2001–2010)
Population 5977 patients aged >50 years with a diagnosis of COPD.
Main outcome measures Hazard ratios for all cause mortality, emergency oral corticosteroid use, and respiratory related hospital admissions calculated through Cox proportional hazard regression after correction for influential covariates.
Results Mean follow-up was 4.35 years, mean age at diagnosis was 69.1 years, and 88% of β blockers used were cardioselective. There was a 22% overall reduction in all cause mortality with β blocker use. Furthermore, there were additive benefits of β blockers on all cause mortality at all treatment steps for COPD. Compared with controls (given only inhaled therapy with either short acting β agonists or short acting antimuscarinics), the adjusted hazard ratio for all cause mortality was 0.28 (95% CI 0.21 to 0.39) for treatment with inhaled corticosteroid, long acting β agonist, and long acting antimuscarinic plus β blocker versus 0.43 (0.38 to 0.48) without β blocker. There were similar trends showing additive benefits of β blockers in reducing oral corticosteroid use and hospital admissions due to respiratory disease. β blockers had no deleterious impact on lung function at all treatment steps when given in conjunction with either a long acting β agonist or antimuscarinic agent
Conclusions β blockers may reduce mortality and COPD exacerbations when added to established inhaled stepwise therapy for COPD, independently of overt cardiovascular disease and cardiac drugs, and without adverse effects on pulmonary function.
Introduction
The presence of cardiovascular disease and chronic obstructive pulmonary disease (COPD) are intertwined because of the risk of smoking induced atherosclerosis in patients with COPD. Despite the proved benefits of β blockers in treating hypertension, ischaemic heart disease, and heart failure, many doctors are reluctant to prescribe β blockers for patients with concurrent COPD.
Historically β blockers have been avoided in asthma because of the risk of acute bronchospasm. These concerns also apply to COPD, with evidence of a reduction in forced expiratory volume in one second (FEV1), increased airway hyperresponsiveness, and inhibition of bronchodilator response to β agonists in patients receiving non-selective β blockers and high doses of cardioselective β blockers.
Despite these concerns, evidence suggests that cardioselective β blockers do not cause an increase in exacerbations, reduction in airway function, or worsening of quality of life in COPD patients. COPD is a highly heterogeneous condition, and the degree of comorbidities present seems to be independent of the degree of airway obstruction. The treatment of comorbid cardiovascular disease in COPD is especially relevant since cardiac failure has been shown to be a leading cause of death in these patients.
In this regard, the use of β blockers in patients with COPD and cardiovascular disease has been shown to reduce mortality. Whether the improved survival seen with β blockers in COPD is purely due to cardiovascular effects has been questioned. Recent evidence suggests that β blockers may improve survival and exacerbations even in COPD patients without cardiovascular disease.
Although cardioselective β blockers have been designed to target β1 adrenoceptors while avoiding β2 adrenoceptors in the lung and elsewhere, so called cardioselective β blockers (such as atenolol and bisoprolol) are only relatively selective and exert significant β2 antagonism at therapeutic doses, though to a lesser extent than non-selective β blockers such as propranolol. Thus, it might be considered counterintuitive to prescribe both β blockers and β agonists in the same patient, even when they are targeting different organs.
Current COPD management guidelines advocate a stepwise approach using long acting bronchodilators (including β agonists) and inhaled corticosteroids to reduce exacerbations and improve symptoms and lung function. With the exception of tiotropium, combination treatments involving long acting bronchodilators and inhaled corticosteroids have failed to show any significant improvement in mortality. We therefore wished to examine the use of β blockers in the management of COPD, assessing their interactions with β agonists and other COPD drug and assess whether they improve mortality, hospital admissions, and exacerbations when added to established treatment for COPD.