The impact of dual bronchodilation on cardiovascular serious adverse events and mortality in COPD: a quantitative synthesis
Received 13 July 2017
Accepted for publication 22 October 2017
Published 5 December 2017 Volume 2017:12 Pages 3469—3485
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Dr Richard Russell
Paola Rogliani,1,2 Maria Gabriella Matera,3 Josuel Ora,2 Mario Cazzola,1 Luigino Calzetta1
1Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy; 2Division of Respiratory Medicine, University Hospital Tor Vergata, Rome, Italy; 3Department of Experimental Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
Objective: Long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) are burdened by the potential risk of inducing cardiovascular serious adverse events (SAEs) in COPD patients. Since the risk of combining a LABA with a LAMA could be greater, we have carried out a quantitative synthesis to investigate the cardiovascular safety profile of LABA/LAMA fixed-dose combinations (FDCs).
Methods: A pair-wise and network meta-analysis was performed by using the data of the repository database ClinicalTrials.gov concerning the impact of approved LABA/LAMA FDCs versus monocomponents and/or placebo on cardiovascular SAEs in COPD.
Results: Overall, LABA/LAMA FDCs did not significantly (P>0.05) modulate the risk of cardiovascular SAEs versus monocomponents. However, the network meta-analysis indicated that aclidinium/formoterol 400/12 µg and tiotropium/olodaterol 5/5 µg were the safest FDCs, followed by umeclidinium/vilanterol 62.5/25 µg which was as safe as placebo, whereas glycopyrronium/formoterol 14.9/9.6, glycopyrronium/indacaterol 15.6/27.5 µg, and glycopyrronium/indacaterol 50/110 µg were the least safe FDCs. No impact on mortality was detected for each specific FDC.
Conclusion: This meta-analysis indicates that LABA/LAMA FDC therapy is characterized by an excellent cardiovascular safety profile in COPD patients. However, the findings of this quantitative synthesis have been obtained from populations that participated in randomized clinical trials, and were devoid of major cardiovascular diseases. Thus, post-marketing surveillance and observational studies may help to better define the real impact of specific FDCs with regard to the cardiovascular risk.
Keywords: COPD, LABA/LAMA FDC, cardiovascular safety, mortality, meta-analysis
Corrigendum for this paper has been published
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