The efficacy and safety of additional treatment with short-acting muscarinic antagonist combined with long-acting beta-2 agonist in stable patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis

BACKGROUND: The rationale for additional treatment with short-acting bronchodilators combined with long-acting bronchodilators for patients with chronic obstructive pulmonary disease (COPD) is not adequately studied. METHODS: We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of a short-acting muscarinic antagonist (SAMA) therapy combined with a long-acting beta-2 agonist (LABA) in patients with stable COPD. Pulmonary function, dyspnea, health-related quality of life, exercise tolerance, physical activity, exacerbations of COPD, and adverse events during regular use were set as outcomes of interest. RESULTS: We included five controlled trials including two sets of publicly available online data without article publications for the meta-analysis. Additional use of SAMA plus LABA showed a significant improvement in the peak response in FEV(1) (mean difference (MD) 98.70 mL, p < .00001), transitional dyspnea index score (MD .85, p = .02), and St George’s Respiratory Questionnaire score (MD -2.00, p = .008) compared to LABA treatment. There was no significant difference in the risk of exacerbation of COPD (p = .20) and only a slight trend of increased severe adverse events (OR: 2.16, p = .08) and cardiovascular events (OR: 2.38, p = .06). CONCLUSION: Additional treatment with SAMA combined with LABA could be a feasible choice due to its efficacy and safety.