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


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 FEV150.1% (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.


CONCLUSIONS
No differences were observed in aPWV-adjusted mean change from baseline for FF/VI 100/25 µg, compared with placebo.
Division of Pulmonary, Allergy and Critical Care Medicine and UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, USA.
Surya P
SP
Bhatt
Division of Pulmonary, Allergy and Critical Care Medicine and UAB Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, USA.
Mark T
MT
Dransfield
Department of Cardiology, Wales Heart Research Institute, Cardiff.
John R
JR
Cockcroft
GSK, Stockley Park, Uxbridge, UK.
Jie
J
Wang-Jairaj
GSK, Stockley Park, Uxbridge, UK.
Dawn A
DA
Midwinter
GSK, Research Triangle Park, NC, USA.
David B
DB
Rubin
GSK, Research Triangle Park, NC, USA.
Catherine A
CA
Scott-Wilson
GSK, Research Triangle Park, NC, USA.
Courtney
C
Crim
D000280:Administration, Inhalation; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects; D001208:Asia; D001592:Benzyl Alcohols / Q000008:administration & dosage* / Q000009:adverse effects; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002722:Chlorobenzenes / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005060:Europe; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D057194:Intention to Treat Analysis; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D063177:Pulse Wave Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D059289:Vascular Stiffness / Q000187:drug effects*; D014797:Vital Capacity
D000730:Androstadienes; D001592:Benzyl Alcohols; D001993:Bronchodilator Agents; D002722:Chlorobenzenes; D004338:Drug Combinations; C000611924:fluticasone furoate-vilanterol trifenatate; C550468:vilanterol
aortic pulse wave velocity; chronic obstructive pulmonary disease; fluticasone furoate; vilanterol