Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 363, k4388

Triple Therapy in the Management of Chronic Obstructive Pulmonary Disease: Systematic Review and Meta-Analysis


Triple Therapy in the Management of Chronic Obstructive Pulmonary Disease: Systematic Review and Meta-Analysis

Yayuan Zheng et al. BMJ.


Objective: To compare the rate of moderate to severe exacerbations between triple therapy and dual therapy or monotherapy in patients with chronic obstructive pulmonary disease (COPD).

Design: Systematic review and meta-analysis of randomised controlled trials.

Data sources: PubMed, Embase, Cochrane databases, and clinical trial registries searched from inception to April 2018.

Eligibility criteria: Randomised controlled trials comparing triple therapy with dual therapy or monotherapy in patients with COPD were eligible. Efficacy and safety outcomes of interest were also available.

Data extraction and synthesis: Data were collected independently. Meta-analyses were conducted to calculate rate ratios, hazard ratios, risk ratios, and mean differences with 95% confidence intervals. Quality of evidence was summarised in accordance with GRADE methodology (grading of recommendations assessment, development, and evaluation).

Results: 21 trials (19 publications) were included. Triple therapy consisted of a long acting muscarinic antagonist (LAMA), long acting β agonist (LABA), and inhaled corticosteroid (ICS). Triple therapy was associated with a significantly reduced rate of moderate or severe exacerbations compared with LAMA monotherapy (rate ratio 0.71, 95% confidence interval 0.60 to 0.85), LAMA and LABA (0.78, 0.70 to 0.88), and ICS and LABA (0.77, 0.66 to 0.91). Trough forced expiratory volume in 1 second (FEV1) and quality of life were favourable with triple therapy. The overall safety profile of triple therapy is reassuring, but pneumonia was significantly higher with triple therapy than with dual therapy of LAMA and LABA (relative risk 1.53, 95% confidence interval 1.25 to 1.87).

Conclusions: Use of triple therapy resulted in a lower rate of moderate or severe exacerbations of COPD, better lung function, and better health related quality of life than dual therapy or monotherapy in patients with advanced COPD.

Study registration: Prospero CRD42018077033.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.


Fig 1
Fig 1
Flow diagram of trial selection
Fig 2
Fig 2
Risk of bias summary for included studies, showing each risk of bias item for every included study
Fig 3
Fig 3
Risk of bias graph presenting each risk of bias item as percentages across all included studies

Similar articles

See all similar articles

Cited by 8 PubMed Central articles

See all "Cited by" articles


    1. GBD 2016 Risk Factors Collaborators Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017;390:1345-422. 10.1016/S0140-6736(17)32366-8 - DOI - PMC - PubMed
    1. Malerba M, Nardin M, Santini G, Mores N, Radaeli A, Montuschi P. Single-inhaler triple therapy utilizing the once-daily combination of fluticasone furoate, umeclidinium and vilanterol in the management of COPD: the current evidence base and future prospects. Ther Adv Respir Dis 2018;12:1753466618760779. 10.1177/1753466618760779. - DOI - PMC - PubMed
    1. Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am J Respir Crit Care Med 2017;195:557-82. 10.1164/rccm.201701-0218PP - DOI - PubMed
    1. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. . - PubMed
    1. Rojas-Reyes MX, García Morales OM, Dennis RJ, Karner C. Combination inhaled steroid and long-acting beta2-agonist in addition to tiotropium versus tiotropium or combination alone for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2016;6:CD008532. - PMC - PubMed

MeSH terms