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 FEV1 (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.