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Comparative efficacy of long-acting muscarinic antagonists in preventing COPD exacerbations: a network meta-analysis and meta-regression

Background: We hypothesized a class effect of currently available long-acting muscarinic antagonists (LAMAs; i.e. tiotropium as a dry powder inhaler or a soft mist inhaler, aclidinium bromide, and glycopyrronium) in preventing chronic obstructive pulmonary disease (COPD) exacerbations. The hypothesis was tested with a network meta-analysis. Methods: Several databases and manufacturer’s websites were searched for relevant clinical trials. Randomized, controlled trials, of at least 12 weeks duration, comparing a LAMA with placebo or another LAMA were included. Moderate-to-severe and severe exacerbations were chosen as the outcome assessment criteria. The data were pooled using network meta-analysis. Results: A total of 27 studies with 48,140 subjects were included. All LAMAs reduced moderate-to-severe exacerbations compared with placebo. However, there were no statistically significant differences in preventing moderate-to-severe or severe exacerbations among LABAs. In a subgroup analysis restricting studies to those that had a minimum of 6 months of treatment, glycopyrronium was associated with the least-effective strategy and aclidinium was associated with the greatest probability of being the best therapy in preventing severe exacerbations. Our meta-regression analysis suggested that the prevention of COPD exacerbations were less effective in studies which allowed concomitant use of a long-acting beta agonist (LABA). Conclusion: All LAMAs were equally effective in preventing moderate-to-severe exacerbations. Aclidinium was associated with the lowest risk for severe exacerbations when treatment duration was 6 months or longer. The concomitant use of LABA may not enhance the efficacy of LAMAs in preventing COPD exacerbations. More studies are needed to further examine above findings.