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6 September 2005 | Volume 143 Issue 5 | Pages 317-326
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.
Design: Randomized, double-blind study.
Setting: 26 Veterans Affairs medical centers.
Patients: 1829 patients with moderate to severe COPD (mean baseline FEV1, 36% predicted).
Intervention: Once-daily tiotropium (18 µg) or placebo for 6 months. Patients otherwise received usual care, except for other anticholinergic bronchodilators.
Measurements: 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.
Limitations: 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.
Editors' Notes
Context
Contribution
Cautions
–The Editors
Author and Article Information
From the Minneapolis Veterans Affairs Medical Center, Minneapolis, Minnesota; Bay Pines Veterans Affairs Medical Center, Bay Pines, Florida; Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia; Birmingham Veterans Affairs Medical Center, Birmingham, Alabama; and Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut.
Acknowledgments: The authors recognize the contributions of the trial investigators, co-investigators, and study staff (Appendix); P. Arnold, B. Caldwell, S. Johnson, J. Tallman, and D. Chow; and the Duke Clinical Research Institute (which managed the data); and the Minnesota Veterans Research Institute (which furnished administrative support for all study centers).
Grant Support: By Boehringer Ingelheim and Pfizer, Inc.
Potential Financial Conflicts of Interest: Employment: L. Korducki, C. Cassino, S. Kesten (Boehringer Ingelheim Pharmaceuticals); Consultancies: D.E. Niewoehner (Boehringer Ingelheim Pharmaceuticals, Chiron Corp., AstraZeneca, Aventis, Sanofi Pasteur), C. Cote (Boehringer Ingelheim Pharmaceuticals); Honoraria: D.E. Niewoehner (Boehringer Ingelheim Pharmaceuticals), K. Rice (Boehringer Ingelheim Pharmaceuticals), J.A.D. Cooper Jr. (Boehringer Ingelheim Pharmaceuticals); Grants received: D.E. Niewoehner (Boehringer Ingelheim Pharmaceuticals, Chiron Corp., Sanofi Pasteur), K. Rice (Boehringer Ingelheim Pharmaceuticals), C. Cote (Boehringer Ingelheim Pharmaceuticals), D. Paulson (Boehringer Ingelheim Pharmaceuticals); Grants pending: C. Cote (Boehringer Ingelheim Pharmaceuticals).
Requests for Single Reprints: Dennis E. Niewoehner, MD, Pulmonary Section (111N), Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, MN 55417; e-mail, niewo001{at}umn.edu.
Current Author Addresses: Drs. Niewoehner and Rice: Pulmonary Section (111N), Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, MN 55417.
Dr. Cote: Respiratory Diseases (111A), Veterans Affairs Medical Center, PO Box 5005, Bay Pines, FL 35294.
Dr. Paulson: Sanofi-Aventis Research, 9 Great Valley Parkway, Malvern, PA 19355.
Dr. Cooper: Veterans Affairs Medical Center, Pulmonary Division/215 THT, 1900 University Boulevard, Birmingham, AL 35294.
Mr. Korducki and Drs. Cassino and Kesten: 900 Ridgebury Road, Ridgefield, CT 06877.
Author Contributions: Conception and design: D.E. Niewoehner, K. Rice, J.A.D. Cooper Jr., S. Kesten.
Analysis and interpretation of the data: D.E. Niewoehner, K. Rice, D. Paulson, J.A.D. Cooper Jr., L. Korducki, C. Cassino, S. Kesten.
Drafting of the article: D.E. Niewoehner, K. Rice, D. Paulson, L. Korducki, C. Cassino, S. Kesten.
Critical revision of the article for important intellectual content: D.E. Niewoehner, K. Rice, C. Cote, D. Paulson, J.A.D. Cooper Jr., C. Cassino, S. Kesten.
Final approval of the article: D.E. Niewoehner, K. Rice, C. Cote, D. Paulson, J.A.D. Cooper Jr., C. Cassino, S. Kesten.
Provision of study materials or patients: K. Rice, D. Paulson, J.A.D. Cooper Jr.
Statistical expertise: L. Korducki.
Obtaining of funding: D.E. Niewoehner, J.A.D. Cooper Jr., S. Kesten.
Administrative, technical, or logistic support: D.E. Niewoehner, C. Cote, C. Cassino, S. Kesten.
Collection and assembly of data: D.E. Niewoehner, D. Paulson. ARTICLE
Prevention of Exacerbations of Chronic Obstructive Pulmonary Disease with Tiotropium, a Once-Daily Inhaled Anticholinergic Bronchodilator
A Randomized Trial
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