Long-acting muscarinic antagonist (LAMA) plus long-acting beta-agonist (LABA) versus LABA plus inhaled corticosteroid (ICS) for stable chronic obstructive pulmonary disease.

backgroundLong-acting beta-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), and inhaled corticosteroids (ICSs) are inhaled medications used to manage chronic obstructive pulmonary disease (COPD). When two classes of medications are required, a LAMA plus an ICS (LABA+ICS) were previously recommended within a single inhaler as the first-line treatment for managing stable COPD in people in high-risk categories. However, updated international guidance recommends a LAMA plus a LABA (LAMA+LABA). This systematic review is an update of a Cochrane Review first published in 2017.

objectivesTo compare the benefits and harms of LAMA+LABA versus LABA+ICS for treatment of people with stable COPD. SEARCH

methodsWe performed an electronic search of the Cochrane Airways Group Specialised Register, ClinicalTrials.gov, and the World Health Organization Clinical Trials Search Portal, followed by handsearches. Two review authors screened the selected articles. The most recent search was run on 10 September 2022. SELECTION CRITERIA: We included parallel or cross-over randomised controlled trials of at least one month's duration, comparing LAMA+LABA and LABA+ICS for stable COPD. We included studies conducted in an outpatient setting and irrespective of blinding. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and evaluated risk of bias. We resolved any discrepancies through discussion. We analysed dichotomous data as odds ratios (ORs), and continuous data as mean differences (MDs), with 95% confidence intervals (CIs) using Review Manager 5. Primary outcomes were: participants with one or more exacerbations of COPD; serious adverse events; quality of life, as measured by the St. George's Respiratory Questionnaire (SGRQ) total score change from baseline; and trough forced expiratory volume in one second (FEV AUTHORS'

conclusionsCombination LAMA+LABA therapy probably holds similar benefits to LABA+ICS for exacerbations and quality of life, as measured by the St George's Respiratory Questionnaire, for people with moderate to severe COPD, but offers a larger improvement in FEV