title: Comparative efficacy of long-acting   muscarinic antagonists in preventing COPD   exacerbations: a network meta-analysis and   meta-regression.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Oba
authors.forename: Nazir A
authors.initials: NA
authors.lastname: Lone
mesh_terms: D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D018727:Muscarinic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists