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  • Title: Comparisons of exacerbations and mortality among LAMA/LABA combinations in stable chronic obstructive pulmonary disease: systematic review and Bayesian network meta-analysis.
    Author: Lee HW, Park J, Jang EJ, Lee CH.
    Journal: Respir Res; 2020 Nov 25; 21(1):310. PubMed ID: 33238986.
    Abstract:
    BACKGROUND: Only few randomized controlled trials (RCTs) for head-to-head comparison have been conducted between various combinations of long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs). Our study was conducted to compare acute exacerbation and all-cause mortality among different LAMA/LABA regimens using Bayesian network meta-analysis (NMA). METHODS: We searched Medline, EMBASE, and the Cochrane library (search date: July 1, 2019). We included parallel-group RCTs comparing LAMA/LABA combinations with other inhaled drugs in the stable COPD for ≥ 48 weeks. Two different network geometries were used. The geometry of network (A) had nodes of individual drugs or their combination, while that of network (B) combined all other treatments except LAMA/LABA into each drug class. This study was prospectively registered in PROSPERO; CRD42019126753. RESULTS: We included 16 RCTs involving a total of 39,065 patients with stable COPD. Six combinations of LAMA/LABA were identified: tiotropium/salmeterol, glycopyrrolate/indacaterol, umeclidinium/vilanterol, tiotropium/olodaterol, aclidinium/formoterol, and glycopyrrolate/formoterol. We found that umeclidinium/vilanterol was associated with a lower risk of total exacerbations than other LAMA/LABAs in the NMA using network (A) (level of evidence: low or moderate). However, the significant differences were not present in the NMA of network (B). There were no significant differences among the LAMA/LABA combinations in terms of the number of moderate to severe exacerbations, all-cause mortality, major adverse cardiovascular events, or pneumonia. CONCLUSIONS: The present NMA including all available RCTs provided that there is no strong evidence suggesting different benefits among LAMA/LABAs in patients with stable COPD who have been followed up for 48 weeks or more. TRIAL REGISTRATION: This study was prospectively registered in PROSPERO; CRD42019126753.
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