- Journal
- RESPIRATORY MEDICINE AND RESEARCH
- Année
- 2022
- Volume
- 82
- Article
- 100968
- Mois
- NOV
- DOI
- 10.1016/j.resmer.2022.100968
Abstract
Introduction: Several studies in COPD have shown a significant and early increase in the risk of cardiovascular mortality attributable to inhaled bronchodilators including long acting b2 agonists (LABAs) and muscarinic antagonists (LAMAs). Cardiac autonomic system impairment may be a potential mechanism involved.Methods: We performed a phase 4, investigator-initiated, prospective, randomized, blinded, cross-over trial (LAB-Card trial -NCT02872090) to evaluate the effect of two LAMAs and one LABA on the cardiac autonomic system in patients with COPD by using three major assessment approaches: heart rate variability (HRV, a pre-dictor of cardiovascular death), baroreflex sensitivity (BRS) and autonomic function (tilt test).Results: 34 patients attended four visits to receive either tiotropium 18mg, glycopyrronium 44mg, indacaterol 150 mg or placebo (lactose) in a randomized order followed by the assessment of HRV and BRS in supine position and after passive rising. Neither LAMAs (tiotropium or glycopyrronium) nor LABA (indacaterol) induced a higher LF/HF ratio (reflect of sympathetic/parasympathetic balance) measured in supine position at rest compared to placebo (primary outcome). Solely indacaterol induced an increase in heart rate com-pared to placebo. No significant differences were observed for HRV and BRS between active drugs and pla-cebo in supine position or after passive rising.Conclusion: We did not found evidence of a deleterious effect of 2 LAMAs and one LABA on the autonomic cardiovascular control in COPD patients. Further investigations are needed to explore mechanisms by which long-acting bronchodilators may increase cardiovascular events in COPD.(c) 2022 SPLF and Elsevier Masson SAS. All rights reserved.