title: Efficacy and safety of fluticasone furoate/vilanterol or tiotropium in subjects with COPD at cardiovascular risk.
abstract: BACKGROUND
  Fluticasone furoate/vilanterol (FF/VI) is a novel, once-daily, inhaled corticosteroid/long-acting β2-agonist combination approved for the treatment of COPD and asthma. We compared the safety and efficacy of FF/VI and tiotropium (TIO) in subjects with moderate-to-severe COPD with greater risk for comorbid cardiovascular disease (CVD).
  
  
  METHODS
  This randomized, blinded, double-dummy, parallel-group study compared a once-daily morning dose of FF/VI 100/25 mcg delivered via ELLIPTA™ with TIO 18 mcg via HandiHaler(®) for 12 weeks in subjects with diagnosed COPD, forced expiratory volume in 1 second (FEV1) 30%-70% predicted, and CVD or CVD risk. The primary endpoint was change from baseline in 24-hour weighted mean FEV1 on Day 84. Other efficacy endpoints included time to onset of bronchodilation, trough FEV1, other spirometry measures, rescue medication use, symptoms, quality of life (St George's Respiratory Questionnaire-COPD [SGRQ-C]), and health status (COPD Assessment Tests [CAT]) measures. Safety endpoints included cardiovascular monitoring, cortisol excretion, COPD exacerbations, and adverse events, including prespecified drug effects.
  
  
  RESULTS
  Both FF/VI and TIO improved the 24-hour weighted mean FEV1 from baseline after 12 weeks with no significant difference between treatments. Other endpoints favored FF/VI for time to onset of bronchodilation, rescue medication use, dyspnea, SGRQ-C and CAT scores, or favored TIO for change from baseline in forced vital capacity and inspiratory capacity. Pneumonia occurred more frequently in the FF/VI group, and two TIO-treated subjects died following cardiovascular events. Other safety measures were similar between groups, and cardiovascular monitoring did not reveal increased CVD risk.
  
  
  CONCLUSIONS
  Both FF/VI and TIO were efficacious in improving lung function in subjects with COPD and comorbid CVD or CVD risk factors, with minor differences in efficacy and safety profiles.
authors.affiliation: Kootenai Health, Coeur d'Alene, ID, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Covelli
authors.affiliation: Clinique de Pneumologie et de Sommeil de Lanaudière, Quebec, Canada.
authors.forename: Bonavuth
authors.initials: B
authors.lastname: Pek
authors.affiliation: Klinische Forschung, Berlin, Germany.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schenkenberger
authors.affiliation: GlaxoSmithKline Inc., Research Triangle Park, Durham, NC, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Scott-Wilson
authors.affiliation: PAREXEL International, Durham, NC, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Emmett
authors.affiliation: GlaxoSmithKline Inc., Research Triangle Park, Durham, NC, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Crim
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; 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; D002318:Cardiovascular Diseases / Q000150:complications*; D002722:Chlorobenzenes / Q000008:administration & dosage / Q000009:adverse effects; D004338:Drug Combinations; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D011788:Quality of Life; D063189:Symptom Assessment / Q000379:methods; D000069447:Tiotropium Bromide / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D001592:Benzyl Alcohols; D001993:Bronchodilator Agents; D002722:Chlorobenzenes; D004338:Drug Combinations; C550468:vilanterol; C523187:fluticasone furoate; D000069447:Tiotropium Bromide
keywords: COPD; ICS/LABA; anticholinergic; cardiovascular disease; fluticasone furoate/vilanterol; tiotropium