Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial.
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.
Niewoehner
Dennis E
DE
Minneapolis Veterans Affairs Medical Center, Minneapolis, Minnesota 55417, USA. niewo001@umn.edu
Rice
Kathryn
K
Cote
Claudia
C
Paulson
Daniel
D
Cooper
J Allen D
JA
Korducki
Larry
L
Cassino
Cara
C
Kesten
Steven
S
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
D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide