title: Tiotropium versus salmeterol for the prevention of exacerbations of COPD.
abstract: BACKGROUND
  Treatment guidelines recommend the use of inhaled long-acting bronchodilators to alleviate symptoms and reduce the risk of exacerbations in patients with moderate-to-very-severe chronic obstructive pulmonary disease (COPD) but do not specify whether a long-acting anticholinergic drug or a β(2)-agonist is the preferred agent. We investigated whether the anticholinergic drug tiotropium is superior to the β(2)-agonist salmeterol in preventing exacerbations of COPD.
  
  
  METHODS
  In a 1-year, randomized, double-blind, double-dummy, parallel-group trial, we compared the effect of treatment with 18 μg of tiotropium once daily with that of 50 μg of salmeterol twice daily on the incidence of moderate or severe exacerbations in patients with moderate-to-very-severe COPD and a history of exacerbations in the preceding year.
  
  
  RESULTS
  A total of 7376 patients were randomly assigned to and treated with tiotropium (3707 patients) or salmeterol (3669 patients). Tiotropium, as compared with salmeterol, increased the time to the first exacerbation (187 days vs. 145 days), with a 17% reduction in risk (hazard ratio, 0.83; 95% confidence interval [CI], 0.77 to 0.90; P<0.001). Tiotropium also increased the time to the first severe exacerbation (hazard ratio, 0.72; 95% CI, 0.61 to 0.85; P<0.001), reduced the annual number of moderate or severe exacerbations (0.64 vs. 0.72; rate ratio, 0.89; 95% CI, 0.83 to 0.96; P=0.002), and reduced the annual number of severe exacerbations (0.09 vs. 0.13; rate ratio, 0.73; 95% CI, 0.66 to 0.82; P<0.001). Overall, the incidence of serious adverse events and of adverse events leading to the discontinuation of treatment was similar in the two study groups. There were 64 deaths (1.7%) in the tiotropium group and 78 (2.1%) in the salmeterol group.
  
  
  CONCLUSIONS
  These results show that, in patients with moderate-to-very-severe COPD, tiotropium is more effective than salmeterol in preventing exacerbations. (Funded by Boehringer Ingelheim and Pfizer; ClinicalTrials.gov number, NCT00563381.).
authors.affiliation: Hospital of the Universities of Giessen and Marburg, Marburg, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Vogelmeier
authors.forename: Bettina
authors.initials: B
authors.lastname: Hederer
authors.forename: Thomas
authors.initials: T
authors.lastname: Glaab
authors.forename: Hendrik
authors.initials: H
authors.lastname: Schmidt
authors.forename: Maureen P M H
authors.initials: MP
authors.lastname: Rutten-van Mölken
authors.forename: Kai M
authors.initials: KM
authors.lastname: Beeh
authors.forename: Klaus F
authors.initials: KF
authors.lastname: Rabe
authors.forename: Leonardo M
authors.initials: LM
authors.lastname: Fabbri
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D000420:Albuterol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018680:Cholinergic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000453:epidemiology; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000517:prevention & control; D000068299:Salmeterol Xinafoate; D012602:Scopolamine Derivatives / Q000009:adverse effects / Q000627:therapeutic use*; D000069447:Tiotropium Bromide
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D005938:Glucocorticoids; D012602:Scopolamine Derivatives; D000068299:Salmeterol Xinafoate; D000420:Albuterol; D000069447:Tiotropium Bromide