A randomized trial of once-daily fluticasone furoate/vilanterol or vilanterol versus placebo to determine effects on arterial stiffness in COPD

Abstract

Introduction

Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality. Elevated arterial stiffness, measured by aortic pulse wave velocity (aPWV), is a cardiovascular risk surrogate and is potentially modifiable by inhaled corticosteroid/long-acting beta₂-agonist combinations in patients with COPD.

Materials and methods

The effects of once-daily inhaled fluticasone furoate/vilanterol (FF/VI) 100/25 µg, VI 25 µg, versus placebo on arterial stiffness in patients with COPD and baseline aPWV ≥11.0 m/s were investigated in a 24-week, multicenter, double-blind, randomized, stratified (by COPD exacerbation history), parallel-group, placebo-controlled trial. Eligible patients were ≥40 years old, with ≥10 pack-year smoking history, forced expiratory volume in 1 s (FEV₁)/forced vital capacity ≤0.70, and post-bronchodilator FEV₁ ≤70% of predicted. Patients with a major cardiovascular event in the previous 6 months/current severe heart failure/uncontrolled hypertension were excluded. Primary endpoint is change from baseline in aPWV after 24 weeks of treatment. Safety analyses included adverse events (AEs).

Results

The intent-to-treat population included 430 patients: FF/VI (n=135), VI (n=154), and placebo (n=141). Patients were predominantly male (79%) and Asian or White (each 48%), with a mean age of 68.5 years (standard deviation [SD] =7.9), percentage predicted post-bronchodilator FEV₁ 50.1% (SD =13.3), and aPWV 13.26 m/s (SD =2.22) at screening. At 24 weeks, mean (standard error [SE]) changes from baseline in aPWV were −1.75 m/s (SE =0.26, FF/VI), −1.95 m/s (SE =0.24, VI), and −1.97 m/s (SE =0.28, placebo). AEs occurred in 57% (FF/VI), 51% (VI), and 41% (placebo) of patients.

Conclusion

No differences were observed in aPWV-adjusted mean change from baseline for FF/VI 100/25 µg, compared with placebo.

Keywords:

• aortic pulse wave velocity
• chronic obstructive pulmonary disease
• fluticasone furoate
• vilanterol

Acknowledgments

The authors would like to acknowledge the work of participating investigators at the study centers; Lori Hall, Lori DeMauro, and Rita Dhuna’s contributions on data management and study operation. Editorial support was provided by Jennifer Lawton, PhD, at Gardiner-Caldwell Communications (Macclesfield, UK) and was funded by GSK.

Disclosure

SPB has received an NIH KL2 Scholarship (1KL2TR001419); MTD has acted as a consultant for GSK, AstraZeneca, and Boston Scientific; JRC has acted as a consultant for GSK, NIVALIS, and Novartis and has received research support from GSK (NCT1656421); JW-J, DAM, DBR, CAS-W, and CC are employees of GSK and hold restricted/unrestricted GSK shares. Study HZC113108 (NCT1336608) was sponsored by GSK. The abstract of this paper was published in the American Thoracic Society International Conference Abstracts, B.23 Cardiovascular and Respiratory Interactions in COPD, Poster Discussion Session, Monday, May 16, 9:00 am to 11:00 am as an abstract with interim findings. The authors report no other conflicts of interest in this work.