Double bronchodilation in chronic obstructive pulmonary disease: a crude analysis from a systematic review

Abstract

Objective

The combination of a long-acting muscarinic antagonist (LAMA) and a long-acting β₂-agonist (LABA) in a single inhaler is a viable treatment option for patients with chronic obstructive pulmonary disease (COPD). Here, we systematically review the current knowledge on double bronchodilation for the treatment of COPD, with a specific focus on its efficacy versus placebo and/or monotherapy bronchodilation.

Methods

A systematic review of clinical trials investigating LABA/LAMA combination therapies was conducted. Articles were retrieved from PubMed, Embase, and Scopus on June 26, 2016. We specifically selected clinical trials with a randomized controlled or crossover design published in any scientific journal showing the following characteristics: 1) comparison of different LABA/LAMA combinations in a single inhaler for patients with COPD, 2) dose approved in Europe, and 3) focus on efficacy (versus placebo and/or bronchodilator monotherapy) in terms of lung function, respiratory symptoms, or exacerbations.

Results

We analyzed 26 clinical trials conducted on 24,338 patients. All LABA/LAMA combinations were consistently able to improve lung function compared with both placebo and bronchodilator monotherapy. Improvements in symptoms were also consistent versus placebo, showing some lack of correlation for some clinical end points and combinations versus monotherapy bronchodilation. Albeit being an exploratory end point, exacerbations showed an improvement with LABA/LAMA combinations over placebo in some trials; however, scarce information was available in comparison with bronchodilator monotherapy in most studies.

Conclusion

Our data show consistent improvements for LABA/LAMA combinations, albeit with some variability (depending on the clinical end point, the specific combination, and the comparison group). Clinicians should be aware that these are average differences. All treatments should be tailored at the individual level to optimize clinical outcomes.

Keywords:

• COPD
• bronchodilators
• efficacy
• systematic review

Acknowledgments

The authors are grateful to the Spanish teams of Novartis, AstraZeneca, GlaxoSmithKline, and Boehringer Ingelheim for reviewing the efficacy data summarized in the study.

Author contributions

JLLC designed the study and performed the initial search and wrote the manuscript; JLLC, CCA, and EMM revised the list of publications and posters. EQG, LCH, and MAA extracted the information from the articles. FOR supervised the final draft of the manuscript. All authors contributed toward data analysis, drafting and critically revising the paper, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

JLLC has received honoraria for lecturing, scientific advice, participation in clinical studies, or writing publications from the following sources (listed in alphabetical order): Almirall, AstraZeneca, Bayer, Boehringer Ingelheim, Cantabria Pharma, Chiesi, Esteve, Faes, Ferrer, GlaxoSmithKline, Menarini, MSD, Novartis, Pfizer, Rovi, and Takeda, and reports no other conflicts of interest in this work. All of the other authors report no conflicts of interest in this work.