Triple versus dual inhaler therapy in moderate-to-severe COPD: A systematic review and meta-analysis of randomized controlled trials.

Journal Article (Systematic Review;Journal Article)


Treatment of chronic obstructive pulmonary disease (COPD) is evolving specially with triple inhaler therapy.


To perform a meta-analysis to ascertain the safety and efficacy of triple inhaler therapy consisting of an inhaled-glucocorticoid (ICS), long-acting muscarinic antagonist (LAMA) and long-acting beta2-agonist (LABA) when compared with dual therapy (ICS-LABA or LAMA-LABA).


We performed an electronic database search to include randomized controlled trials (RCTs) comparing between triple and dual inhalers. Pooled rate-ratio (RR) or odds-ratio (OR) for dichotomous data and weighted mean difference (MD) for continuous data were calculated with their corresponding 95% confidence interval (CI).


Our study included 12 RCTs totaling 19,322 patients, mean age of 65 ± 8.2 years and 68.2% were male. Pooled analysis demonstrated a significant reduction in moderate-to-severe COPD exacerbations with triple therapy (RR 0.75; 95% CI 0.69-0.83; P < 0.01). Additionally, triple therapy caused significant increase in trough FEV1 (MD 0.09 L; 95% CI 0.07-0.12; P < 0.01), significant reduction in the mean St. George's Respiratory Questionnaire (SGRQ) score (MD -1.67; 95% CI -2.02- -1.31; P < 0.01), and more patients experienced ≥ 4 points reduction of SGRQ score (OR 1.27; 95% CI 1.19-1.35; P < 0.01). Triple therapy was associated with an increased risk of pneumonia when compared to LABA/LAMA (OR 1.25; 95% 1.03-1.97; P = 0.03) but there were no significant differences in other adverse events between triple and dual inhalers.


Among patients with moderate-to-severe COPD, triple inhaler therapy was associated with a reduction of moderate-to-severe COPD exacerbations, improved lung function and improved quality of life when compared to dual inhaler therapy but with an increased pneumonia risk.

Full Text

Duke Authors

Cited Authors

  • Zayed, Y; Barbarawi, M; Kheiri, B; Haykal, T; Chahine, A; Rashdan, L; Hamid, K; Sundus, S; Banifadel, M; Aburahma, A; Bachuwa, G; Chandran, A

Published Date

  • July 2019

Published In

Volume / Issue

  • 13 / 7

Start / End Page

  • 413 - 428

PubMed ID

  • 30947394

Electronic International Standard Serial Number (EISSN)

  • 1752-699X

International Standard Serial Number (ISSN)

  • 1752-6981

Digital Object Identifier (DOI)

  • 10.1111/crj.13026


  • eng