title: Long-acting Muscarinic Antagonist Versus Inhaled Corticosteroid when Added to Long-acting β-agonist for COPD: A Meta-analysis.
abstract: The purpose of this study was to systematically review the efficacy and safety of long-acting β-agonist/long-acting muscarinic antagonist (LABA/LAMA) and LABA/inhaled corticosteroid (ICS) combinations in patients with advanced chronic obstructive pulmonary disease (COPD). Randomized clinical trials of at least 12 weeks of duration comparing LABA/LAMA and LABA/ICS combinations were included. We chose forced expiratory volume in 1 second (FEV1), St. George's Respiratory Questionnaire (SGRQ) score, Transitional Dyspnea Index (TDI), COPD Assessment Test (CAT) score, COPD exacerbations, mortality, and other safety parameters as outcome assessment criteria. We included six randomized controlled trials with a total of 4,319 patients. Most patients did not have a history of exacerbation. LABA/LAMA was associated with greater improvement in FEV1than LABA/ICS (mean difference (MD) 0.09L, 95%confidence interval (CI) 0.07 to 0.11L; high certainty). Two treatments appeared clinically equivalent in improving SGRQ (MD -0.12, 95%CI -1.16 to 0.92; high certainty), TDI (MD 0.15, 95%CI -0.05 to 0.35; high certainty), and CAT scores (MD 0.28 95%CI -0.29 to 0.85; moderate certainty). LABA/LAMA was associated with an absolute reduction of approximately 8% in the incidence of pneumonia compared with LABA/ICS (risk ratio 0.41, 95%CI 0.18 to 0.94; moderate certainty). There was no significant difference in safety and exacerbation outcomes. However, equivalence of two treatments could not be concluded due to imprecision especially for mortality, cardiac serious adverse events, and severe exacerbations. Our findings support the use of dual long-acting bronchodilators for patients with advanced COPD but without frequent exacerbations given the excess risk of pneumonia with LABA/ICS.
authors.affiliation: a Division of Pulmonary, Critical Care, and Environmental Medicine, School of Medicine, University of Missouri , Columbia , Missouri , USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Oba
authors.affiliation: a Division of Pulmonary, Critical Care, and Environmental Medicine, School of Medicine, University of Missouri , Columbia , Missouri , USA.
authors.forename: Arul V
authors.initials: AV
authors.lastname: Chandran
authors.affiliation: a Division of Pulmonary, Critical Care, and Environmental Medicine, School of Medicine, University of Missouri , Columbia , Missouri , USA.
authors.forename: Joe V
authors.initials: JV
authors.lastname: Devasahayam
mesh_terms: D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use*; D000318:Adrenergic beta-Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D018727:Muscarinic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index
chemical_list: D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D003692:Delayed-Action Preparations; D018727:Muscarinic Antagonists
keywords: Bronchodilator agents; drug-related side effects and adverse reactions; outcome assessment (health care); pneumonia; quality of life; respiratory function tests