title: Effect of fluticasone propionate/salmeterol (250/50 microg) or salmeterol (50 microg) on COPD exacerbations.
abstract: OBJECTIVE
  COPD exacerbations are associated with significant morbidity and mortality. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/salmeterol 250/50 and salmeterol 50 microg twice daily on moderate to severe exacerbations.
  
  
  METHODS
  Patients received standardized treatment with fluticasone propionate/salmeterol 250/50 during a 1-month run-in, followed by randomization to fluticasone propionate/salmeterol 250/50 or salmeterol for 12 months. Moderate to severe exacerbations were defined as worsening symptoms of COPD requiring treatment with oral corticosteroids, antibiotics, or hospitalization.
  
  
  RESULTS
  In 782 patients with COPD (mean FEV(1)=0.94+/-0.36 L, 33% predicted normal), treatment with fluticasone propionate/salmeterol 250/50 significantly reduced (1) the annual rate of moderate to severe exacerbations by 30.5% compared with salmeterol (1.06 and 1.53 per subject per year, respectively, p<0.001), (2) the risk of time to first exacerbation by 25% (hazard ratio=0.750, p=0.003) and (3) the annual rate of exacerbations requiring oral corticosteroids by 40% (p<0.001). Clinical improvements observed during run-in treatment with fluticasone propionate/salmeterol 250/50 were better maintained over 12 months with fluticasone propionate/salmeterol 250/50 than salmeterol. Adverse events were reported for a similar percentage of subjects across groups. A higher reporting of pneumonia was observed with fluticasone propionate/salmeterol 250/50 than salmeterol (7% vs. 4%).
  
  
  CONCLUSIONS
  We conclude that fluticasone propionate/salmeterol 250/50 is more effective than salmeterol at reducing the rate of moderate to severe exacerbations over 1 year. The benefits of this reduction relative to the risk of a higher incidence of reported pneumonia should be considered. This study supports the use of fluticasone propionate/salmeterol 250/50 for the reduction of COPD exacerbations in patients with COPD.
authors.affiliation: Pulmonary Research Institute of Southeast Michigan, 28807 Eight Mile Road, Suite 103, Livonia, MI 48152, USA. garytferguson@msn.com
authors.forename: Gary T
authors.initials: GT
authors.lastname: Ferguson
authors.forename: Antonio
authors.initials: A
authors.lastname: Anzueto
authors.forename: Richard
authors.initials: R
authors.lastname: Fei
authors.forename: Amanda
authors.initials: A
authors.lastname: Emmett
authors.forename: Katharine
authors.initials: K
authors.lastname: Knobil
authors.forename: Christopher
authors.initials: C
authors.lastname: Kalberg
mesh_terms: D000328:Adult; D000368:Aged; D000420:Albuterol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D011788:Quality of Life; D000068299:Salmeterol Xinafoate; D012907:Smoking / Q000009:adverse effects
chemical_list: D000730:Androstadienes; D001993:Bronchodilator Agents; D004338:Drug Combinations; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol