title: Formoterol mono- and combination therapy with tiotropium in patients with COPD: a 6-month study.
abstract: Although guidelines recommend combining long-acting bronchodilators in COPD, data are limited. We examined the clinical efficacy and safety of formoterol, tiotropium and the combination in patients with COPD. Eight hundred and forty-seven patients with COPD (mean FEV(1) 52% predicted; FEV(1)/FVC 53%) were randomized to receive one of the following four treatments for 24 weeks: formoterol 10 microg b.i.d. plus tiotropium 18 microg o.d.; formoterol 10 microg b.i.d.; tiotropium 18 microg o.d., or placebo. The study was partially blinded (formoterol and placebo). For the primary endpoint, FEV(1) 2h post-dose after 24 weeks, there were small differences in favour of the combination therapy versus formoterol (0.07 L, p=0.044) or tiotropium (0.06 L, p=0.066). All three treatments were superior to placebo (p<0.001). The combination was statistically superior to monotherapy for: the primary endpoint (p=0.044 vs. formoterol); FEV(1) 5 min after the first dose (p<0.001) and at 12 weeks (p<0.05 vs. tiotropium); and peak expiratory flow averaged over the first 6 weeks (p<0.001 vs. both). The three active treatments were significantly more effective than placebo for secondary endpoints: COPD-related 'bad days', symptoms, use of rescue medication and peak expiratory flow, and aspects of health-related quality of life. The overall incidence of adverse events was similar with all active treatments, although COPD-related adverse events were more common with tiotropium. Combined bronchodilator therapy may be a valuable treatment option for patients with COPD.
authors.affiliation: Klinik für Innere Medizin mit Schwerpunkt Pneumologie, Universitätsklinikum Giessen und Marburg, Standort Marburg Baldingerstrasse, D-35043 Marburg, Germany. claus.vogelmeier@med.uni-marburg.de
authors.forename: Claus
authors.initials: C
authors.lastname: Vogelmeier
authors.forename: Peter
authors.initials: P
authors.lastname: Kardos
authors.forename: Sergio
authors.initials: S
authors.lastname: Harari
authors.forename: Steven J M
authors.initials: SJ
authors.lastname: Gans
authors.forename: Stephan
authors.initials: S
authors.lastname: Stenglein
authors.forename: Jackie
authors.initials: J
authors.lastname: Thirlwell
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D011788:Quality of Life / Q000523:psychology; D012602:Scopolamine Derivatives / Q000008:administration & dosage*; D013147:Spirometry / Q000379:methods; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D004983:Ethanolamines; D012602:Scopolamine Derivatives; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide