Dual bronchodilators in chronic obstructive pulmonary disease: Evidence from randomized controlled trials and real-world studies

Purpose: Dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting β₂-agonist (LABA) is recommended in the pharmacological management of chronic obstructive pulmonary disease (COPD) according to the Global Initiative for Chronic Obstructive Lung Disease. To better understand the evidence supporting use of LAMA+LABA therapy in COPD and evaluate consistency within and across clinical research study types, we systematically reviewed and analyzed data from both randomized controlled trials (RCTs) and real-world studies. Methods: We searched PubMed from inception until April 4, 2019, for phase 2/3/4 RCTs of ≥24 weeks’ duration and real-world studies in which the efficacy and/or safety of LAMA+LABAs were compared with monotherapies, other LAMA+LABAs, LABA+inhaled corticosteroid (ICS), or triple therapy (LAMA+LABA+ICS). We extracted primary and key secondary outcomes data from relevant articles for descriptive purposes. Results: Overall, 24 RCTs and 8 real-world studies were included in the analysis based on predefined inclusion criteria. LAMA+LABAs improved lung function and health-related quality of life, and reduced exacerbation rates and dyspnea when compared with monotherapies, LABA+ICS, or triple therapy in both RCTs and real-world studies. Importantly, all LAMA+LABAs were well tolerated, with their safety profiles comparable to those of respective monotherapies, and had lower incidences of pneumonia than ICS-containing regimens. Conclusion: Results of RCTs and real-world studies are largely consistent; demonstrate that LAMA+LABAs improve lung function and health-related quality of life and reduce exacerbation rates and dyspnea relative to other available pharmacotherapies; and reinforce the position of LAMA+LABAs in the pharmacological management of COPD.