Background: Patients with COPD often require multiple
therapies to improve lung function and decrease symptoms and
exacerbations. Salmeterol and theophylline are indicated for the
treatment of COPD, but the use of these agents in combination has not
been extensively studied.
Objectives: To compare the
efficacy and safety of salmeterol plus theophylline vs either agent
alone in COPD.
Methods: Randomized, double-blind,
double-dummy, parallel-group trial in 943 patients with COPD. After an
open-label theophylline titration period (serum levels, 10 to 20μ
g/mL), patients were randomly assigned to receive salmeterol (42μ
g bid) plus theophylline, salmeterol (42 μg bid), or theophylline
for 12 weeks. Serial pulmonary function tests were completed on day 1
and treatment week 12. Patients kept diary cards and noted their peak
flow rates, symptom scores, and albuterol use, and periodically
completed quality-of-life and dyspnea questionnaires.
Results: All three groups significantly improved compared
with baseline. Combination treatment with salmeterol plus theophylline
provided significantly (p ≤ 0.045) greater improvements in pulmonary
function; significantly (p ≤ 0.048) greater decreases in symptoms,
dyspnea, and albuterol use; and significantly fewer COPD exacerbations
(p = 0.023 vs theophylline). In general, treatment with salmeterol
provided greater improvement in lung function and satisfaction with
treatment compared with theophylline. Salmeterol treatment was also
associated with significantly fewer drug-related adverse events
(p ≤ 0.042) than either treatment that included theophylline. The
safety profile (adverse events, vital signs, and ECG findings) of the
two treatments that included theophylline were similar.
Conclusion: Patients with COPD may benefit from combination
treatment with salmeterol plus theophylline, without a resulting
increase in adverse events or other adverse