Effect of long-acting beta-agonists on the frequency of COPD exacerbations: a meta-analysis

What is Known and Objective: Inhaled long-acting beta-agonists have been licensed for the treatment of chronic obstructive pulmonary disease (COPD) since the late 1990s, and they improve lung function and symptoms of dyspnoea. However, the evidence that long-acting beta-agonists alone can reduce the rate of COPD exacerbations is not conclusive. This meta-analysis was performed to evaluate their effect on the frequency of exacerbations. Methods: MEDLINE, EMBASE, CINAHL and the Cochrane trials database were searched for the review. Randomized controlled trials of greater than or equal to 24 weeks' treatment duration comparing long-acting beta-agonists (LABAs) with placebo were reviewed. Studies were pooled to yield odds ratios (ORs) with 95% confidence intervals (CIs). Results and Discussion: Seventeen randomized controlled trials (11871 randomized subjects) met the inclusion criteria and were selected for analysis. Salmeterol, formoterol and indacaterol significantly reduced COPD exacerbations compared with placebo. Salmeterol significantly reduced COPD exacerbations with both study arms exposed or not exposed to inhaled corticosteroids (ICS). The summary ORs were 0 79 (95% CI: 0 67-0 92; P < 0 01) and 0 80 (95% CI: 0 65-0 99; P = 0 04), respectively. However, when both arms were not exposed to ICS, there was no significant reduction in exacerbations with formoterol compared with placebo. The ' summary OR was 0 93 (95% CI: 0 75-1 15; P = 0 50). What is New and Conclusion: Long-acting beta-agonists reduce the frequency of COPD exacerbations. Salmeterol, formoterol and indacaterol significantly reduced COPD exacerbations compared with placebo. Salmeterol but not formoterol decreased exacerbations significantly in the absence of ICS.