Comparisons of exacerbations and mortality among LAMA/LABA combinations in stable chronic obstructive pulmonary disease:
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RESEARCH
Comparisons of exacerbations and mortality among LAMA/LABA combinations in stable chronic obstructive pulmonary disease: systematic review and Bayesian network meta‑analysis Hyun Woo Lee1, Jimyung Park2, Eun Jin Jang3 and Chang‑Hoon Lee2*
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 regi‑ mens using Bayesian network meta-analysis (NMA). Methods: We searched Medline, EMBASE, and the Cochrane library (search date: July 1, 2019). We included parallelgroup 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 combi‑ nation, 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, allcause mortality, major adverse cardiovascular events, or pneumonia. Conclusions: The present NMA including all available RCTs provided that there is no strong evidence suggesting dif‑ ferent 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. Keywords: Pulmonary disease, Chronic obstructive, Respiratory therapy, Administration, Inhalation, Symptom flare-up, Mortality, Drug-related side effects and adverse reactions, Bayes theorem, Network meta-analysis
*Correspondence: [email protected] 2 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak‑Ro Jongno‑Gu, Seoul 03080, Republic of Korea Full list of author information is available at the end of the article
Background Long acting bronchodilators such as long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs) are the main drugs used to treat stable
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