Impact of Mucolytic Agents on COPD Exacerbations: A Pair-wise and Network Meta-analysis

Mucolytics are potentially useful for the management of chronic obstructive pulmonary disease (COPD), although there is conflicting advice on their use in different guideline documents. Furthermore, there is paucity of data comparing the efficacy of the different mucolytic agents in reducing the odds of COPD exacerbations. We performed pair-wise and network meta-analyses to evaluate the impact of mucoly-tics in COPD. Randomized clinical trials lasting at least 3 months and investigating the effects of mucolytics on COPD exacerbations were identified from published studies and repository databases. Mucolytics significantly reduced the odds of exacerbation vs. placebo (11 studies analyzed: odds ratio (OR) 0.51, 95% confidence interval (CI) 0.39-0.67; p < 0.001). The most effective drugs were carbocysteine, erdosteine, and N-acetylcysteine 1,200 mg/day (SUCRA 68.0-79.0%), whereas the OR was similar to placebo for ambroxol and N-acetylcysteine 600 mg/day. Only N-acetylcysteine 1,200 mg/day significantly protected against exacerbations vs. placebo (2 studies analyzed: OR 0.56, 95% CI 0.35-0.92; p < 0.05; high quality of evidence). A signal of effectiveness was detected for carbocysteine (2 studies analyzed: OR 0.45, 95% CI 0.20-1.01; p ≥ 0.05; moderate quality of evidence). Specific differences in study designs and patient-related characteristics, such as history of exacerbations and ethnicity, were potential effect modifiers for our statistical models, whereas neither respiratory function nor the use of corticosteroids influenced the analysis. This meta-analysis demonstrates that mucolytics are useful in preventing COPD exacerbations as maintenance add-on therapy to patients with frequent exacerbations. The effectiveness of mucolytics is independent of the severity of airway obstruction and the use of inhaled corticosteroids.