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16 September 2008 | Volume 149 Issue 6 | Pages 380-390
Background: Concerns exist regarding increased risk for mortality associated with some chronic obstructive pulmonary disease (COPD) medications.
Objective: To examine the association between various respiratory medications and risk for death in veterans with newly diagnosed COPD.
Design: Nested case–control study in a cohort identified between 1 October 1999 and 30 September 2003 and followed through 30 September 2004 by using National Veterans Affairs inpatient, outpatient, pharmacy, and mortality databases; Centers for Medicare & Medicaid Services databases; and National Death Index Plus data. Cause of death was ascertained for a random sample of 40% of those who died during follow-up. Case patients were categorized on the basis of all-cause, respiratory, or cardiovascular death. Mortality risk associated with medications was assessed by using conditional logistic regression adjusted for comorbid conditions, health care use, and markers of COPD severity.
Setting: U.S. Veterans Health Administration health care system.
Participants: 32 130 case patients and 320 501 control participants in the all-cause mortality analysis. Of 11 897 patients with cause-of-death data, 2405 case patients had respiratory deaths and 3159 case patients had cardiovascular deaths.
Measurements: All-cause mortality; respiratory and cardiovascular deaths; and exposure to COPD medications, inhaled corticosteroids, ipratropium, long-acting β-agonists, and theophylline in the 6 months preceding death.
Results: Adjusted odds ratios (ORs) for all-cause mortality were 0.80 (95% CI, 0.78 to 0.83) for inhaled corticosteroids, 1.11 (CI, 1.08 to 1.15) for ipratropium, 0.92 (CI, 0.88 to 0.96) for long-acting β-agonists, and 1.05 (CI, 0.99 to 1.10) for theophylline. Ipratropium was associated with increased cardiovascular deaths (OR, 1.34 [CI, 1.22 to 1.47]), whereas inhaled corticosteroids were associated with reduced risk for cardiovascular death (OR, 0.80 [CI, 0.72 to 0.88]). Results were consistent across sensitivity analyses.
Limitations: Current smoking status and lung function were not measured. Misclassification of cause-specific mortality is unknown.
Conclusion: The possible association between ipratropium and elevated risk for all-cause and cardiovascular death needs further study.
Editors' Notes
Context
Contribution
Caution
Implication
—The Editors
Author and Article Information
From the Hines Veterans Affairs Hospital, Hines, Illinois; Northwestern University Feinberg School of Medicine, Chicago, Illinois; University of Illinois at Chicago, Chicago, Illinois; Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, Washington; and the American Board of Medical Specialties, Evanston, Illinois.
Note: At the time of this work, Dr. Weiss was at the Center for Management of Complex Chronic Care, Hines Veterans Affairs Hospital, and the Institute for Healthcare Studies, Northwestern University Feinberg School of Medicine. He has since moved to the American Board of Medical Specialties.
Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the U.S. Department of Veterans Affairs.
Grant Support: By the U.S. Department of Veterans Affairs Health Services Research and Development (IIR 03-307).
Potential Financial Conflicts of Interest: Honoraria: T.A. Lee (AstraZeneca, Novartis), D.H. Au (GlaxoSmithKline). Consultancies: K.B. Weiss (Merck & Co.). Stock ownership or options (other than mutual funds): D.H. Au (Pfizer). Grants received: T.A. Lee (Altana, Aventis, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Merck & Co., Novartis, Pfizer, Schering-Plough, Sepracor, University of Kentucky). Other: D.H. Au (Assessing the Impact of Recent Updates for Advair and Serevent Special Issues Board).
Reproducible Research Statement: Study protocol and data set: Not available. Statistical code: Available from Dr. Lee (todd.lee{at}va.gov).
Requests for Single Reprints: Todd A. Lee, PharmD, PhD, Hines Veterans Affairs Hospital, 5000 South 5th Avenue (151-H), Hines, IL 60141; e-mail, todd.lee{at}va.gov.
Current Author Addresses: Dr. Lee and Mr. Bartle: Hines Veterans Affairs Hospital, 5000 South 5th Avenue (151-H), Hines, IL 60141.
Dr. Pickard: 833 South Wood Street, RM164 MC886, Chicago, IL 60612.
Dr. Au: Veterans Affairs Puget Sound Health Care System, Health Services Research and Development (152), 1660 South Columbian Way, Seattle, WA 98108.
Dr. Weiss: American Board of Medical Specialties, 1007 Church Street, Suite 404, Evanston, IL 60201-5913.
Author Contributions: Conception and design: T.A. Lee, D.H. Au, K.B. Weiss.
Analysis and interpretation of the data: T.A. Lee, A.S. Pickard, D.H. Au, B. Bartle, K.B. Weiss.
Drafting of the article: T.A. Lee, A.S. Pickard, D.H. Au, K.B. Weiss.
Critical revision of the article for important intellectual content: T.A. Lee, A.S. Pickard, D.H. Au, B. Bartle, K.B. Weiss.
Final approval of the article: T.A. Lee, A.S. Pickard, D.H. Au, B. Bartle, K.B. Weiss.
Statistical expertise: T.A. Lee, A.S. Pickard.
Obtaining of funding: T.A. Lee.
Administrative, technical, or logistic support: B. Bartle.
Collection and assembly of data: A.S. Pickard, B. Bartle. ARTICLE
Risk for Death Associated with Medications for Recently Diagnosed Chronic Obstructive Pulmonary Disease
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