Journal of General Internal Medicine

, Volume 21, Issue 10, pp 1011–1019

Meta-analysis: Anticholinergics, but not β-agonists, reduce severe exacerbations and respiratory mortality in COPD

  • Shelley R. Salpeter
  • Nicholas S. Buckley
  • Edwin E. Salpeter
Original Articles

DOI: 10.1111/j.1525-1497.2006.00507.x

Cite this article as:
Salpeter, S.R., Buckley, N.S. & Salpeter, E.E. J GEN INTERN MED (2006) 21: 1011. doi:10.1111/j.1525-1497.2006.00507.x


BACKGROUND: Anticholinergics and β2-agonists have generally been considered equivalent choices for bronchodilation in chronic obstructive pulmonary disease (COPD).

OBJECTIVE: To assess the safety and efficacy of anticholinergics and β2-agonists in COPD.

DESIGN: We comprehensively searched electronic databases from 1966 to December 2005, clinical trial websites, and references from selected reviews. We included randomized controlled trials of at least 3 months duration that evaluated anticholinergic or β2-agonist use compared with placebo or each other in patients with COPD.

MEASUREMENTS: We evaluated the relative risk (RR) of exacerbations requiring withdrawal from the trial, severe exacerbations requiring hospitalization, and deaths attributed to a lower respiratory event.

RESULTS: Pooled results from 22 trials with 15,276 participants found that anticholinergic use significantly reduced severe exacerbations (RR 0.67, confidence interval [CI] 0.53 to 0.86) and respiratory deaths (RR 0.27, CI 0.09 to 0.81) compared with placebo. β2-Agonist use did not affect severe exacerbations (RR 1.08, CI 0.61 to 1.95) but resulted in a significantly increased rate of respiratory deaths (RR 2.47, CI 1.12 to 5.45) compared with placebo. There was a 2-fold increased risk for severe exacerbations associated with β2-agonists compared with anticholinergics (RR 1.95, CI 1.39 to 2.93). The addition of β2-agonist to anticholinergic use did not improve any clinical outcomes.

CONCLUSION: Inhaled anticholinergics significantly reduced severe exacerbations and respiratory deaths in patients with COPD, while β2-agonists were associated with an increased risk for respiratory deaths. This suggests that anticholinergics should be the bronchodilator of choice in patients with COPD, and β2-agonists may be associated with worsening of disease control.

Key words

chronic obstructive pulmonary disease COPD adrenergic β-agonists cholinergic antagonists muscarinic antagonists meta-analysis clinical outcomes mortality 
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Copyright information

© Society of General Internal Medicine 2006

Authors and Affiliations

  • Shelley R. Salpeter
    • 1
    • 2
  • Nicholas S. Buckley
    • 3
  • Edwin E. Salpeter
    • 4
  1. 1.Department of MedicineStanford University School of MedicineStanfordUSA
  2. 2.Department of MedicineSanta Clara Valley Medical CenterSan JoseUSA
  3. 3.International Baccalaureate ProgramSequoia High SchoolRedwood CityUSA
  4. 4.Center for Radiophysics and Space ResearchCornell UniversityIthacaUSA

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