title: Long-acting bronchodilators and arterial stiffness in patients with COPD: a comparison of fluticasone furoate/vilanterol with tiotropium.
abstract: BACKGROUND
  Increased arterial stiffness as measured by aortic pulse wave velocity (aPWV) predicts cardiovascular events and mortality and is elevated in patients with COPD. Prior investigation suggests that a long-acting β-agonist (LABA)/inhaled corticosteroid (ICS) lowers aPWV in patients with baseline aPWV ≥ 11 m/s. This study compared the effect of the ICS/LABA fluticasone furoate/vilanterol (FF/VI), 100/25 μg, delivered via the ELLIPTA dry powder inhaler, with tiotropium bromide (TIO), 18 μg, on aPWV.
  
  
  METHODS
  This multicenter, randomized, blinded, double-dummy, parallel-group, 12-week study compared FF/VI and TIO, both administered once daily. The primary end point was aPWV change from baseline at 12 weeks. Safety end points included adverse events (AEs), vital signs, and clinical laboratory tests.
  
  
  RESULTS
  Two hundred fifty-seven patients with COPD and aPWV ≥ 11 m/s were randomized; 87% had prior cardiovascular events and/or risk. The mean difference in aPWV between FF/VI and TIO at week 12 was not significant (P = .484). Because the study did not contain a placebo arm, a post hoc analysis was performed to show that both treatments lowered aPWV by an approximate difference of 1 m/s compared with baseline. The proportion of patients reporting AEs was similar with FF/VI (24%) and TIO (18%). There were no changes in clinical concern for vital signs or clinical laboratory tests.
  
  
  CONCLUSIONS
  No differences on aPWV were observed between FF/VI and TIO. However, further studies with a placebo arm are required to establish definitively whether long-acting bronchodilators lower aPWV. Both treatments demonstrated an acceptable tolerability profile.
  
  
  BACKGROUND
  ClinicalTrials.gov; No.: NCT01395888; URL: www.clinicaltrials.gov.
authors: University Grenoble Alpes, Grenoble University Hospital, Grenoble, France.
authors: Jean-Louis
authors: JL
authors: Pepin
authors: Wales Heart Research Institute, Cardiff University, Cardiff, Wales.
authors: John R
authors: JR
authors: Cockcroft
authors: GlaxoSmithKline, Stockley Park, England.
authors: Dawn
authors: D
authors: Midwinter
authors: GlaxoSmithKline, Research Triangle Park, Durham, NC.
authors: Sanjay
authors: S
authors: Sharma
authors: GlaxoSmithKline, Research Triangle Park, Durham, NC.
authors: David B
authors: DB
authors: Rubin
authors: Georg-August-Universitat Göttingen, Göttingen, Germany. Electronic address: stefan.andreas@med.uni-goettingen.de.
authors: Stefan
authors: S
authors: Andreas
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects; 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; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000188:drug therapy*; D063177:Pulse Wave Analysis / Q000379:methods; D012129:Respiratory Function Tests; D012602:Scopolamine Derivatives / Q000008:administration & dosage* / Q000009:adverse effects; D012720:Severity of Illness Index; D000069447:Tiotropium Bromide; D016896:Treatment Outcome; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D000730:Androstadienes; D001592:Benzyl Alcohols; D001993:Bronchodilator Agents; D002722:Chlorobenzenes; D003692:Delayed-Action Preparations; D012602:Scopolamine Derivatives; C550468:vilanterol; C523187:fluticasone furoate; D000069447:Tiotropium Bromide