Comparisons of exacerbations and mortality among LAMA/LABA combinations in stable chronic obstructive pulmonary disease: systematic review and Bayesian network meta-analysis

Hyun Woo Lee,Jimyung Park,Chang-Hoon Lee,Eun Jin Jang

doi:10.1186/s12931-020-01540-8

Abstract

BackgroundOnly 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).MethodsWe 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.ResultsWe 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.ConclusionsThe 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.

Highlights

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)
Data synthesis and analysis The present Bayesian network meta-analysis (NMA) was conducted using a random effects model with a heterogeneous variance structure [36, 37] because we found more than two LAMA/ LABA therapy regimens and assumed that the variance of the odds ratios of individual treatment (LAMA/LABA) compared with baseline treatment (Tiotropium) was different
After a full-text review, we found 16 articles that met the eligibility criteria of the present systematic review (SR)

Summary

Introduction

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 regi‐ mens using Bayesian network meta-analysis (NMA). Long acting bronchodilators such as long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs) are the main drugs used to treat stable. Lee et al Respir Res (2020) 21:310 chronic obstructive pulmonary disease (COPD). They improve symptoms and exercise performance status by reducing small airway limitations, hyperinflation [1, 2], and exacerbation risk [3,4,5]. In patients with stable COPD whose symptoms or exacerbations cannot be controlled using a single long-acting bronchodilator, LAMA/LABA combination therapy is primarily recommended [17]

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Discussion

Conclusion