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Relationship of inhaled long-acting bronchodilators with cardiovascular outcomes among patients with stable COPD: a meta-analysis and systematic review of 43 randomized trials

Authors Li CX, Cheng WK, Guo J, Guan W

Received 14 December 2018

Accepted for publication 22 February 2019

Published 11 April 2019 Volume 2019:14 Pages 799—808

DOI https://doi.org/10.2147/COPD.S198288

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Chunxue Bai


Chenxi Li,1 Wenke Cheng,2 Jin Guo,1 Wei Guan1

1Department of Respiratory, Affiliated Hospital of Qinghai University, Xining, People’s Republic of China; 2Department of Cardiology, Affiliated Hospital of Qinghai University, Xining, People’s Republic of China

Background: Long-acting muscarinic antagonists (LAMAs) and long-acting β2–agonists (LABAs) are the mainstay of maintenance therapy for chronic obstructive pulmonary disease (COPD). Although previous studies have supported inhaled long-acting bronchodilators (ILABs) for overall cardiovascular safety, the risk of specific cardiovascular outcomes such as arrhythmia, heart failure and stroke is still unknown.
Materials and methods: We systematically searched from PubMed, the Embase database and the Cochrane Library for published studies on ILABs and COPD, from its inception to November 10, 2018, with no language restrictions. The RRs and corresponding 95% CIs were pooled to evaluate ILAB/placebo.
Results: Finally, 43 randomized controlled trials were included. Compared with placebo, ILABs do not increase the risk of overall and specific cardiovascular adverse events (AEs); on the contrary, they can reduce the incidence of hypertension (RR 0.73, 95% CI 0.55–0.98;I2,19.9%; P= 0.221). However, when stratified according to the specific agents of ILABs, olodaterol might reduce the risk of overall cardiovascular adverse events (OCAEs) (RR 0.65, 95% CI 0.49–0.88;I2,27.5%; P= 0.000), and the protective effect of lowing blood pressure disappeared. Similarly, the use of inhaled LABA might increase the risk of cardiac failure (RR 1.71, 95% CI 1.04–2.84;I2,0%; P= 0.538), but this risk disappeared when stratified according to the specific agents of LABA. Besides, formoterol might decrease the risk of cardiac ischemia (RR 0.53, 95% CI 0.32–0.91; I2,0%; P= 0.676).
Conclusions: Overall, the use of ILABs was not associated with overall cardiovascular AEs in patients with stable COPD. When stratified according to the specific agents of LABA, olodaterol might reduce the risk of OCAE; and formoterol might decrease the risk of cardiac ischemia. LABA might reduce the incidence of hypertension, but might increase the risk of heart failure. Therefore, COPD patients with a history of heart failure should use it with caution.

Keywords: bronchodilators, long-acting muscarinic antagonists, long-acting β2–agonists, adverse events, meta-analysis


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