Combining tiotropium and salmeterol in COPD: Effects on airflow obstruction and symptoms

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Clinical information on 24-h spirometric efficacy of combining tiotropium and salmeterol compared to single-agent therapy is lacking in patients with COPD. Methods: A randomized, double-blind, four-way crossover study of 6-week treatment periods comparing combination therapy of tiotropium 18 microg plus QD or bid salmeterol 50 microg versus single-agent therapy. Serial 24-h spirometry (FEV(1), FVC), effects on dyspnea (TDI focal score), and rescue salbutamol use were evaluated in 95 patients.

Results: Tiotropium plus QD salmeterol was superior to tiotropium or salmeterol alone in average FEV(1) (0-24h) by 72 mL and 97 mL (p<0.0001), respectively. Compared to this QD regimen, combination therapy including bid salmeterol provided comparable daytime (0-12h: 12 mL, p=0.38) bronchodilator effects, but significantly more bronchodilation during the night-time (12-24h: 73 mL, 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. Conclusion: 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.

Writer: J A van Noord