Study Examines Mortality Risk Associated with Respiratory Medications in Veterans with Newly Diagnosed COPD

AUTHOR/FUNDING INFORMATION:
This study was funded by HSR&D. Drs. Lee and Pickard and Mr. Bartle are part of HSR&D's Center for the Management of Complex Chronic Care in Hines, IL. At the time of this study, Dr. Weiss was also part of this HSR&D Center of Excellence.

BACKGROUND:
Concerns exist regarding increased mortality risk for some chronic obstructive pulmonary disease (COPD) medications. This nested, case-control observational study examined the association between COPD medication use and risk of mortality in veterans with newly diagnosed COPD. Data from observational studies may provide evidence of longer-term benefits and harms associated with medications, particularly in patients with COPD who tend to be elderly and have multiple co-morbidities, and especially since relatively rare adverse events may not be detected in shorter-term clinical trials. Using VA, Medicare and Medicaid data, investigators assessed all-cause, respiratory, and cardiovascular-related deaths among veterans ages 45 and older who used VA healthcare and were diagnosed with COPD between 10/1/99 and 9/30/03. Controls (n=320,501) used in this study were individually matched to cases (n=32,130) on sex, age, region of the country, and year of diagnosis; cause of death data were matched for 11,897 veterans. Medications assessed included: inhaled corticosteroids, ipratropium, long-acting beta-agonists, and theophylline.

FINDINGS:

• With respect to all-cause mortality, ipratropium and ipratropium plus theophylline were associated with elevated risk of death, while inhaled corticosteroids were associated with reduced mortality.
• With respect to cardiovascular-related mortality, ipratropium exposure was associated with a 34% increase in the odds of cardiovascular death, while inhaled corticosteroid exposure was associated with a 20% decrease. Long-acting beta-agonists and theophylline were not associated with statistically significant risks in cardiovascular-related deaths.
• Theophylline was associated with an increased risk of respiratory death, while inhaled corticosteroids were associated with a 15% reduction in respiratory death.

LIMITATIONS:

• This study did not measure current smoking status and lung function.
• Observational studies are susceptible to bias due to confounders (e.g., disease severity).
• The results of this study may not be applicable to veterans with more severe COPD.

Lee T, Pickard A, Au D, Bartle B, Weiss K. Risk of Deaths Associated with Medications for Recently Diagnosed COPD: A Nested Case-Control Study. Annals of Internal Medicine 2008 Sep 16;149(6):380-90.