Cardio-selective and non-selective beta-blockers in chronic obstructive pulmonary disease: effects on bronchodilator response and exercise

Intern Med J. 2010 Mar;40(3):193-200. doi: 10.1111/j.1445-5994.2009.01943.x. Epub 2009 Mar 10.

Abstract

Background: Patients with chronic obstructive pulmonary disease (COPD) often have co-existing cardiovascular disease and may require beta-blocker treatment. There are limited data on the effects of beta-blockers on the response to inhaled beta2-agonists and exercise capacity in patients with COPD.

Objective: To determine the effects of different doses of cardio-selective and non-selective beta-blockers on the acute bronchodilator response to beta-agonists in COPD, and to assess their effects on exercise capacity.

Methods: A double-blind, randomized, three-way cross-over (metoprolol 95 mg, propranolol 80 mg, placebo) study with a final open-label high-dose arm (metoprolol 190 mg). After 1 week of each treatment, the bronchodilator response to salbutamol was measured after first inducing bronchoconstriction using methacholine. Exercise capacity was assessed using the incremental shuttle walk test.

Results: Eleven patients with moderate COPD were recruited. Treatments were well-tolerated although two did not participate in the high-dose metoprolol phase. The area under the salbutamol-response curve was lower after propranolol compared with placebo (P=0.0006). The area under the curve also tended to be lower after high-dose metoprolol (P=0.076). The per cent recovery of the methacholine-induced fall was also lower after high-dose metoprolol (P=0.0018). Low-dose metoprolol did not alter the bronchodilator response. Oxygen saturation at peak exercise was lower with all beta-blocker treatments (P=0.046).

Conclusion: Non-selective beta-blockers and high doses of cardio-selective beta-blockers may inhibit the bronchodilator response to beta2-agonists in patients with COPD. Beta-blockers were also associated with lower oxygen saturation during exercise. The clinical significance of these adverse effects is uncertain in view of the benefits of beta-blocker treatment for cardiovascular disease.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-Agonists / pharmacology
  • Adrenergic beta-Agonists / therapeutic use
  • Adrenergic beta-Antagonists / pharmacology
  • Adrenergic beta-Antagonists / therapeutic use*
  • Aged
  • Bronchoconstriction / drug effects*
  • Bronchoconstriction / physiology
  • Bronchodilator Agents / pharmacology
  • Bronchodilator Agents / therapeutic use*
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Interactions / physiology
  • Exercise* / physiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology

Substances

  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Bronchodilator Agents