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

BACKGROUND: Anticholinergics and beta 2-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 beta 2-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 beta 2-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. beta 2-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 beta 2-agonists compared with anticholinergics (RR 1.95, CI 1.39 to 2.93). The addition of beta 2-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 beta 2-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 beta 2-agonists may be associated with worsening of disease control.