Chest
Volume 149, Issue 5, May 2016, Pages 1181-1196
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Original Research: COPD
A Systematic Review With Meta-Analysis of Dual Bronchodilation With LAMA/LABA for the Treatment of Stable COPD

https://doi.org/10.1016/j.chest.2016.02.646Get rights and content

Background

The wide availability of long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) fixed-dose combinations (FDCs) in the absence of head-to-head comparative pragmatic trials makes it difficult to choose which combination should be used. Therefore, we carried out a systematic review with meta-analysis that incorporated the data from trials lasting at least 3 months to evaluate the effectiveness of LAMA/LABA FDCs for COPD treatment.

Methods

Randomized controlled trials were identified by searching different databases of published and unpublished trials. We aimed to assess the influence of LAMA/LABA combinations on trough FEV1, transitional dyspnea index, St. George's Respiratory Questionnaire, and cardiac safety vs monocomponents.

Results

Fourteen papers and one congress abstract with 23,168 patients with COPD (combinations, n = 10,328; monocomponents, n = 12,840) were included in this study. Our results showed that all LAMA/LABA combinations were always more effective than the LAMA or LABA alone in terms of the improvement in trough FEV1. Although there was not significant difference among LAMA/LABA combinations, we identified a gradient of effectiveness among the currently available LAMA/LABA FDCs. LAMA/LABA combinations also improved both transitional dyspnea index and St. George's Respiratory Questionnaire scores, but did not increase the cardiovascular risk when compared with monocomponents.

Conclusions

The gradient of effectiveness emerging from this meta-analysis is merely a weak indicator of possible differences between the various LAMA/LABA FDCs. Only direct comparisons will document if a specific LAMA/LABA FDC is better than the other. In the meanwhile, we believe it is only proper to consider that dual bronchodilation is better than a LAMA or a LABA alone, regardless of the drugs used.

Section snippets

Searching Strategy

This systematic review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement (Fig 1).9

We performed a comprehensive literature search for RCTs lasting at least 3 months and concerning the influence of treatment with LABAs and LAMAs administered in combination in patients suffering from COPD diagnosed by pulmonary function testing.1, 10

The terms “chronic obstructive pulmonary disease” and “COPD” were included for the disease; the

Study Characteristics

Results obtained from 23,168 patients with COPD (combinations, n = 10,328; monocomponents, n = 12,840) were selected from 14 published papers and one abstract presented at the European Respiratory Society Congress (Amsterdam, 2015) that reported 22 RCTs. Two studies (two RCTs) used aclidinium and formoterol,27, 28 three studies (six RCTs) used tiotropium and olodaterol,29, 30, 31 four studies (five RCTs) used glycopyrronium and indacaterol,32, 33, 34, 35 five studies (seven RCTs) used

Discussion

The main finding of this meta-analysis is that, regardless of the LAMA/LABA combination examined, dual bronchodilation was always more effective than the LAMA or LABA alone in terms of the improvement in trough FEV1. All LAMA/LABA combinations also improved TDI and SGRQ scores compared with monocomponents, although the impact of the different LAMA/LABA combinations on patient-reported outcomes has not always been examined, or at least described, in a complete manner in the available reports,

Acknowledgments

Author contributions: M. C. contributed to study conception and design, drafting the submitted article and revising it critically for important intellectual content, and providing final approval of the version to be published. L. C. contributed to acquisition, analysis, and interpretation of data; drafting the submitted article and revising it critically for important intellectual content; and providing final approval of the version to be published. P. R. and M. G. M. contributed to acquisition

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    FUNDING/SUPPORT: The Department of Systems Medicine of the University of Rome Tor Vergata was funded by Almirall, Novartis, and Zambon, and is funded by Boehringer Ingelheim to conduct research in the respiratory field.

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