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Detrimental effects of beta-blockers in COPD: a concern for nonselective beta-blockers
Hanneke J van der Woude1, Johan Zaagsma, Dirkje S Postma
1Department of Pulmonary Diseases, Martini Hospital, Van Ketwich Verschuurlaan 82, 9721 SW Groningen, the Netherlands. jvbhw@home.nl
Insights
Beta-blockers like propranolol and metoprolol can worsen airway hyperresponsiveness (AHR) in COPD patients, while celiprolol does not. Propranolol also reduced FEV(1) and formoterol
Area of Science:
- Pulmonary Medicine
- Cardiology
- Pharmacology
Background:
- Beta-blockers are known to exacerbate FEV(1) and airway hyperresponsiveness (AHR) in asthma patients.
- COPD outcomes are influenced by FEV(1) and AHR, and cardiac comorbidities often necessitate beta-blocker use.
Purpose of the Study:
- To evaluate the impact of different beta-blockers on AHR, FEV(1), and bronchodilator response in COPD patients.
- To compare the pulmonary effects of propranolol, metoprolol, and celiprolol against a placebo.
Main Methods:
- A double-blind, placebo-controlled, randomized, cross-over study involving 15 patients with mild-to-moderate COPD and AHR.
- Patients received propranolol, metoprolol, celiprolol, or placebo for 4 days, with assessments of FEV(1) and AHR (PC(20)) on day 4.
- The response to formoterol (a beta(2)-agonist) was measured after beta-blocker administration.
Main Results:
- Propranolol and metoprolol significantly increased AHR (decreased PC(20)) compared to placebo and celiprolol.
- FEV(1) decreased only with propranolol treatment.
- Propranolol impaired the bronchodilating effect of formoterol, while metoprolol and celiprolol did not.
Conclusions:
- Celiprolol demonstrated no adverse pulmonary effects in COPD patients.
- Propranolol and metoprolol increased AHR, with propranolol also reducing FEV(1) and blunting the response to formoterol.
- The choice of beta-blocker in COPD patients requires balancing cardiovascular benefits against potential detrimental pulmonary effects on FEV(1), AHR, and bronchodilator response.
Introduction:
beta-Blockers are known to worsen FEV(1) and airway hyperresponsiveness (AHR) in patients with asthma. Both characteristics determine the outcome of COPD, a disease with frequent cardiac comorbidity requiring beta-blocker treatment.
Objective:
To determine the effects of beta-blockers on AHR (provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)]), FEV(1), and response to formoterol in patients with COPD.
Design:
A double-blind, placebo-controlled, randomized, cross-over study.
Setting:
An ambulatory, hospital outpatient clinic of pulmonary diseases.
Patients:
Patients with mild-to-moderate irreversible COPD and AHR.
Intervention:
Fifteen patients received propranolol (80 mg), metoprolol (100 mg), celiprolol (200 mg), or placebo for 4 days, followed by a washout period >/= 3 days. On day 4 of treatment, FEV(1) and PC(20) were assessed. Immediately hereafter, formoterol (12 microg) was administered and FEV(1) was measured for up to 30 min.
Results:
PC(20) was significantly lower (p < 0.01) with propranolol and metoprolol treatment (geometric means, 2.06 mg/mL and 2.02 mg/mL, respectively) than with placebo (3.16 mg/mL) or celiprolol (3.41 mg/mL). FEV(1) deteriorated only after propranolol treatment (2.08 +/- 0.31 L) [mean +/- SD] compared with placebo (2.24 +/- 0.37 L). The fast bronchodilating effect of formoterol was hampered by propranolol (mean increase in FEV(1) at 3 min, 6.7 +/- 8.9%) but was unaffected by the other beta-blockers (16.9 +/- 9.8%, 22 +/- 11.6%, and 16.9 +/- 9.0% for placebo, metoprolol, and celiprolol, respectively).
Conclusions:
Pulmonary effects did not occur by celiprolol. Only propranolol reduced FEV(1) and the bronchodilating effect of formoterol. Both metoprolol and propranolol increased AHR. Thus, different classes of beta-blockers have different pulmonary effects. The anticipated beneficial cardiovascular effects of a beta-blocker must be weighted against the putative detrimental pulmonary effects, ie, effect on FEV(1), AHR, and response to additional beta(2)-agonists.
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