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Can Fam Physician
Vol. 53, No. 9, September 2007, pp.1429 - 1430
Copyright © 2007 by The College of Family Physicians of Canada
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Debates

Rebuttal: Should we avoid β-agonists for moderate and severe chronic obstructive pulmonary disease?

NO

Shawn D. Aaron, MD
Dr Salpeter argues that monotherapy with β-agonists might be dangerous for patients with asthma. This could be true; however, the question being debated concerns β-agonist use for chronic obstructive pulmonary disease (COPD), not for asthma. Many large clinical trials and properly done metaanalyses1 have confirmed that β-agonists are extremely effective at improving lung function, relieving dyspnea, improving quality of life, and preventing exacerbations among patients with COPD.2,3 Recent large clinical trials have also confirmed that βagonists are safe for patients with COPD.

The 1 meta-analysis that diverges from all of the rest is the meta-analysis done by Dr Salpeter.4 This meta-analysis had serious flaws. Only 4 published trials studying β-agonists were included, even though more than 15 trials were available in the literature. Furthermore, the authors did not attempt to obtain mortality data from many of the pivotal randomized controlled trials published on this subject. The 4 trials included in the meta-analysis contained duplicate publications. Sixty percent of the results of the Salpeter meta-analysis came from the results of only 1 study. The results of this meta-analysis are simply unreliable.

The TORCH (Towards a Revolution in COPD Health) trial, a randomized double-blind placebo-controlled clinical trial, unequivocally showed that 1521 COPD patients treated with the long-acting β-agonist salmeterol for 3 years had a slightly greater (but not statistically significant) chance of survival over 3 years than 1524 patients treated with placebo had (hazard ratio 0.88, 95% confidence interval [CI] 0.73 to 1.06).5 Many more patients were included in the TORCH trial then were included in the entire Salpeter meta-analysis of 4 studies. In addition, patients treated with fluticasone-salmeterol combination products showed a 3-year survival benefit compared with patients given placebo (hazard ratio 0.83, 95% CI 0.68 to 1.00). Patients treated with either salmeterol or fluticasone-salmeterol combinations had improved lung function, improved quality of life, and 15% to 25% fewer exacerbations than those treated with placebo. Therefore long-acting β-agonists and inhaled steroid–long-acting β-agonist combination products appear to improve lung function and quality of life, decrease exacerbations, and also slightly improve survival. They unquestionably do not kill people with COPD!

Footnotes

These rebuttals are responses from the authors who were asked to discuss whether β-agonists should be avoided for moderate and severe chronic obstructive pulmonary disease in the Debates section of the August issue (Can Fam Physician 2007;53:1290–3 [Eng], 1294–7 [Fr]).

References

  1. Appleton S, Poole P, Smith B, Veale A, Lasserson T, Chan M. Long-acting beta 2-agonists for poorly reversible chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2006;3:CD001104.[Medline]
  2. Stockley RA, Chopra N, Rich L. Addition of salmeterol to existing treatment in patients with COPD: a 12 month study. Thorax 2006;61:122-8.[Abstract/Free Full Text]
  3. Rennard SI, Anderson W, ZuWallck R, Broughton J, Bailey W, Friedman M, et al. Use of a long-acting inhaled β2-adrenergic agonist, salmeterol xinafoate, in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001;163:1087-92.[Abstract/Free Full Text]
  4. Salpeter SR, Buckley NS, Salpeter EE. Meta-analysis: anticholinergics, but not beta-agonists, reduce severe exacerbations and respiratory mortality in COPD. J Gen Intern Med 2006;21:1011-9.[Medline]
  5. Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007;356:775-89.[Abstract/Free Full Text]




This Article
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