title: Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial.
abstract: BACKGROUND
  Patients with chronic obstructive pulmonary disease (COPD) frequently develop exacerbations, leading to major clinical and health resource use ramifications.
  
  
  OBJECTIVE
  To prospectively evaluate the effectiveness of a long-acting inhaled anticholinergic bronchodilator, tiotropium, in reducing COPD exacerbations and exacerbation-related health care utilization.
  
  
  METHODS
  Randomized, double-blind study.
  
  
  METHODS
  26 Veterans Affairs medical centers.
  
  
  METHODS
  1829 patients with moderate to severe COPD (mean baseline FEV(1), 36% predicted).
  
  
  METHODS
  Once-daily tiotropium (18 microg) or placebo for 6 months. Patients otherwise received usual care, except for other anticholinergic bronchodilators.
  
  
  METHODS
  The coprimary end points were the percentage of patients with a COPD exacerbation and the percentage of patients with a COPD-related hospitalization.
  
  
  RESULTS
  Tiotropium significantly reduced the percentage of patients experiencing 1 or more exacerbations compared with placebo (27.9% vs. 32.3%, respectively; difference, -5.7 percentage points [95% CI, -10.4 to -1.0 percentage points]; P = 0.037). Fewer tiotropium patients were hospitalized because of COPD exacerbation (7.0% vs. 9.5%, respectively; difference, -3.0 percentage points [CI, -5.9 to -0.1 percentage points]; P = 0.056), although this difference was of borderline statistical significance. Analysis of secondary outcomes indicates that tiotropium may lengthen the time to first COPD exacerbation (P = 0.028) and reduce health care utilization for exacerbations, including the frequency of hospitalizations (P = 0.047), unscheduled clinic visits (P = 0.019), and days of antibiotic treatment (P = 0.015). Tiotropium did not statistically significantly reduce all-cause hospitalization rates.
  
  
  CONCLUSIONS
  Trial participants were enrolled from 1 health care system, and 99% were men. The follow-up period extended for only 6 months.
  
  
  CONCLUSIONS
  Tiotropium reduces COPD exacerbations and may reduce related health care utilization in patients with moderate to severe COPD.
authors.affiliation: Minneapolis Veterans Affairs Medical Center, Minneapolis, Minnesota 55417, USA. niewo001@umn.edu
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Niewoehner
authors.forename: Kathryn
authors.initials: K
authors.lastname: Rice
authors.forename: Claudia
authors.initials: C
authors.lastname: Cote
authors.forename: Daniel
authors.initials: D
authors.lastname: Paulson
authors.forename: J Allen D
authors.initials: JA
authors.lastname: Cooper
authors.forename: Larry
authors.initials: L
authors.lastname: Korducki
authors.forename: Cara
authors.initials: C
authors.lastname: Cassino
authors.forename: Steven
authors.initials: S
authors.lastname: Kesten
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018680:Cholinergic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012602:Scopolamine Derivatives / Q000008:administration & dosage* / Q000009:adverse effects; D000069447:Tiotropium Bromide; D017211:Treatment Failure
chemical_list: D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide