SAN FRANCISCO – Patients with chronic obstructive pulmonary disease do worse when their regimens include theophylline or ipratropium, according to two poster presentations by Todd A. Lee, Pharm.D., at the International Conference of the American Thoracic Society.
In the first study, ipratropium (Atrovent) was associated with an adjusted 45% increased relative risk of death over 2.5 years, and theophylline was associated with an adjusted 23% increased relative risk of death, wrote Dr. Lee and his colleagues at Northwestern University, Chicago.
On the other hand, the use of inhaled corticosteroids was associated with an adjusted 13% decrease in the relative risk of death.
In the second study, all patients taking multidrug regimens that included theophylline had significantly higher mortality rates than did patients taking the same regimen without theophylline.
For example, the adjusted increased relative risk of death of a regimen including inhaled corticosteroids, long-acting β-agonists, and theophylline was 31% compared with a regimen including just inhaled corticosteroids and long-acting β-agonists.
In many of the regimens, the addition of theophylline also was associated with a significant increase in the rate of chronic obstructive pulmonary disease exacerbations.
Both of the studies involved a retrospective analysis of patients with chronic obstructive pulmonary disease in the Veterans Affairs health care system, Dr. Lee explained.
The first study used a random sample of 7,840 of these patients, and the second study used all 169,842 patients divided into six treatment groups based on their medication regimens.
Each of the treatment groups included at least 10,000 patients.
The results were adjusted for age, the chance that patients were receiving theophylline at baseline, and COPD exacerbations in the preceding 6 months.
The ipratropium finding is consistent with other studies that have raised concerns about the safety of this agent, the investigators wrote.
Tiotropium (Spiriva), a similar anticholinergic, has recently been introduced, the investigators noted.
Regarding theophylline, the investigators noted that their studies did not include quality of life measures or the potential benefits of theophylline on the activities of daily living.
“However,” they wrote, “in order to justify the use of theophylline in patients with COPD it would have to have substantial benefits in those areas to overcome the potential risk that may be associated with the use of this medication.”
Dr. Lee disclosed that he is the recipient of research grants from a consortium of pharmaceutical companies for investigations involving chronic obstructive pulmonary disease.