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Randomized controlled trials and real-world observational studies in evaluating cardiovascular safety of inhaled bronchodilator therapy in COPD

Authors Kardos P, Worsley S, Singh D, Román-Rodríguez M, Newby DE, Müllerová H

Received 3 August 2016

Accepted for publication 20 October 2016

Published 25 November 2016 Volume 2016:11(1) Pages 2885—2895

DOI https://doi.org/10.2147/COPD.S118867

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr Richard Russell


Peter Kardos,1 Sally Worsley,2 Dave Singh,3 Miguel Román-Rodríguez,4 David E Newby,5 Hana Müllerová2

1Group Practice and Respiratory, Allergy and Sleep Unit, Red Cross Maingau Hospital, Frankfurt, Germany; 2GSK, Stockley Park, Middlesex, 3University of Manchester, Medicines Evaluation Unit, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK; 4Primary Care Respiratory Research Unit, Instituto de Investigación Sanitaria de Palma IdisPa, Palma de Mallorca, Spain; 5BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen’s Medical Research Institute, Edinburgh, UK


Abstract:
Long-acting muscarinic antagonist (LAMA) or long-acting β2-agonist (LABA) bronchodilators and their combination are recommended for the maintenance treatment of chronic obstructive pulmonary disease (COPD). Although the efficacy of LAMAs and LABAs has been well established through randomized controlled trials (RCTs), questions remain regarding their cardiovascular (CV) safety. Furthermore, while the safety of LAMA and LABA monotherapy has been extensively studied, data are lacking for LAMA/LABA combination therapy, and the majority of the studies that have reported on the CV safety of LAMA/LABA combination therapy were not specifically designed to assess this. Evaluation of CV safety for COPD treatments is important because many patients with COPD have underlying CV comorbidities. However, severe CV and other comorbidities are often exclusion criteria for RCTs, contributing to a lack in external validity and generalizability. Real-world observational studies are another important tool to evaluate the effectiveness and safety of COPD therapies in a broader population of patients and can improve upon the external validity limitations of RCTs. We examine what is already known regarding the CV and cerebrovascular safety of LAMA/LABA combination therapy from RCTs and real-world observational studies, and explore the advantages and limitations of data derived from each study type. We also describe an ongoing prospective, observational, comparative post-authorization safety study of a LAMA/LABA combination therapy (umeclidinium/vilanterol) and LAMA monotherapy (umeclidinium) versus tiotropium, with a focus on the relative merits of the study design.

Keywords: real-world observational study, cardiovascular, cerebrovascular, safety, umeclidinium, vilanterol

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