• Luigino Calzetta, Mario Cazzola, Maria Gabriella Matera, and Paola Rogliani.
• Department of Experimental Medicine, Unit of Respiratory Medicine, University of Rome "Tor Vergata," Rome, Italy.
• Chest. 2019 Apr 1; 155 (4): 758-770.

BackgroundInhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) combination is commonly prescribed to treat COPD; therefore, we performed a meta-analysis on the effect of adding a long-acting muscarinic receptor antagonist (LAMA) to ICS/LABA combination in COPD.MethodsStudies were identified by searching in different databases the randomized controlled trials that investigated the effect of ICS/LABA/LAMA combination in COPD. The primary end points were the effect of triple therapy on trough FEV1, risk of acute exacerbation of COPD (AECOPD), and risk of cardiovascular serious adverse events (SAEs), compared with ICS/LABA combination. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assess the quality of evidence.ResultsThirteen randomized controlled trials including 15,519 patients with COPD (ICS/LABA/LAMA combination, 53.1%; ICS/LABA combination, 46.9%) were meta-analyzed. ICS/LABA/LAMA combination improved trough FEV1 (mean difference, +104.86 mL; 95% CI, 86.74-122.99; high quality of evidence) and protected against AECOPD (relative risk, 0.78; 95% CI, 0.71-0.85; high quality of evidence) vs ICS/LABA combination. For every approximately four patients treated with triple therapy, one increased FEV1 > 100 mL, and approximately 26 patients had to be treated for 1 year with ICS/LABA/LAMA combination to prevent one AECOPD, compared with ICS/LABA combination. Adding a LAMA to ICS/LABA therapy did not modulate the risk of cardiovascular SAEs (moderate quality of evidence).ConclusionsTriple therapy provides significant clinical benefit in patients with COPD on ICS/LABA combination. ICS/LABA therapy can be escalated to triple therapy without a real risk to increase cardiovascular SAEs when a LAMA is added to the combination.Trial RegistryClinicalTrials.gov; No.: CRD42018095300; URL: www.clinicaltrials.gov.Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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