Clinical information on 24-h spirometric efficacy of combining tiotropium and salmeterol compared to single-agent therapy is lacking in patients with COPD.

A randomized, double-blind, four-way crossover study of 6-week treatment periods comparing combination therapy of tiotropium 18μg plus qd or bid salmeterol 50μg versus single-agent therapy. Serial 24-h spirometry (FEV₁, FVC), effects on dyspnea (TDI focal score) and rescue salbutamol use were evaluated in 95 patients.

Tiotropium plus qd salmeterol was superior to tiotropium or salmeterol alone in average FEV₁ (0–24h) by 72mL and 97mL (p<0.0001), respectively. Compared to this qd regimen, combination therapy including bid salmeterol provided comparable daytime (0–12h: 12mL, p=0.38) bronchodilator effects, but significantly more bronchodilation during the night-time (12–24h: 73mL, p<0.0001). Clinically relevant improvements in TDI focal score were achieved with bronchodilator combinations including salmeterol qd or bid (2.56 and 2.71; p<0.005 versus components). Symptom benefit of combination therapies was also reflected in less need for reliever medication. All treatments were well tolerated.

Compared to single-agent therapy, combination therapy of tiotropium plus salmeterol in COPD provided clinically meaningful improvements in airflow obstruction and dyspnea as well as a reduction in reliever medication.