Once daily long-acting beta2-agonists and long-acting muscarinic antagonists in a combined inhaler versus placebo for chronic obstructive pulmonary disease

• Published in: Cochrane database of systematic reviews 2019-03, Vol.3 (3), p.CD012930
• Main Authors: Maqsood, Usman, Ho, Terence N, Palmer, Karen, Eccles, Fiona Jr, Munavvar, Mohammed, Wang, Ran, Crossingham, Iain, Evans, David Jw
• Format: Article
• Language: English
• Subjects: Adrenergic beta-2 Receptor Agonists - administration & dosage; Adrenergic beta-2 Receptor Agonists - adverse effects; Aged; Cause of Death; Chronic obstructive pulmonary disease, stable ‐ pharmacotherapy; Cross-Over Studies; Disease Progression; Drug Administration Schedule; Drug Combinations; Humans; Lungs & airways; Middle Aged; Muscarinic Antagonists - administration & dosage; Muscarinic Antagonists - adverse effects; Nebulizers and Vaporizers; Placebos - administration & dosage; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - mortality; Quality of Life; Randomized Controlled Trials as Topic
• ISSN: 1469-493X
• DOI: 10.1002/14651858.CD012930.pub2

Chronic obstructive pulmonary disease (COPD) is a respiratory condition causing accumulation of mucus in the airways, cough, and breathlessness; the disease is progressive and is the fourth most common cause of death worldwide. Current treatment strategies for COPD are multi-modal and aim to reduce morbidity and mortality and increase patients' quality of life by slowing disease progression and preventing exacerbations. Fixed-dose combinations (FDCs) of a long-acting beta -agonist (LABA) plus a long-acting muscarinic antagonist (LAMA) delivered via a single inhaler are approved by regulatory authorities in the USA, Europe, and Japan for the treatment of COPD. Several LABA/LAMA FDCs are available and recent meta-analyses have clarified their utility versus their mono-components in COPD. Evaluation of the efficacy and safety of once-daily LABA/LAMA FDCs versus placebo will facilitate the comparison of different FDCs in future network meta-analyses. We assessed the evidence for once-daily LABA/LAMA combinations (delivered in a single inhaler) versus placebo on clinically meaningful outcomes in patients with stable COPD. We identified trials from Cochrane Airways' Specialised Register (CASR) and also conducted a search of the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch). We searched CASR and trial registries from their inception to 3 December 2018; we imposed no restriction on language of publication. We included parallel-group and cross-over randomised controlled trials (RCTs) comparing once-daily LABA/LAMA FDC versus placebo. We included studies reported as full-text, those published as abstract only, and unpublished data. We excluded very short-term trials with a duration of less than 3 weeks. We included adults (≥ 40 years old) with a diagnosis of stable COPD. We included studies that allowed participants to continue using their ICS during the trial as long as the ICS was not part of the randomised treatment. Two review authors independently screened the search results to determine included studies, extracted data on prespecified outcomes of interest, and assessed the risk of bias of included studies; we resolved disagreements by discussion with a third review author. Where possible, we used a random-effects model to meta-analyse extracted data. We rated all outcomes using the GRADE (Grades of