Study objectives: To examine and compare the efficacy
and safety of salmeterol xinafoate, a long-acting inhaledβ
2-adrenergic agonist, with inhaled ipratropium bromide
and inhaled placebo in patients with COPD.
stratified, randomized, double-blind, double-dummy, placebo-controlled,
parallel group clinical trial.
Setting: Multiple sites
at clinics and university medical centers throughout the United
Patients: Four hundred eleven symptomatic
patients with COPD with FEV1 ≤ 65% predicted and no
clinically significant concurrent disease.
Interventions: Comparison of inhaled salmeterol (42 μg
twice daily), inhaled ipratropium bromide (36 μg four times a day),
and inhaled placebo (2 puffs four times a day) over 12 weeks.
Results: Salmeterol xinafoate was significantly
(p < 0.0001) better than placebo and ipratropium in improving lung
function at the recommended doses over the 12-week trial. Both
salmeterol and ipratropium reduced dyspnea related to activities of
daily living compared with placebo; this improvement was associated
with reduced use of supplemental albuterol. Analyses of time to first
COPD exacerbation revealed salmeterol to be superior to placebo and
ipratropium (p < 0.05). Adverse effects were similar among the three
Conclusions: These collective data support
the use of salmeterol as first-line bronchodilator therapy for the
long-term treatment of airflow obstruction in patients with
Abbreviations: AUC = area under the
curve; BDI = baseline dyspnea index; CRDQ = chronic respiratory
disease questionnaire; HRQL = health-related quality of life;
6MW = 6-min walk; TDI = transition dyspnea index