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

van Noord, J.A.; Aumann, J.-L.; Janssens, E.; Smeets, J.J.; Zaagsma, J.; Mueller, A.; Cornelissen, P.J.G.

doi:10.1016/j.rmed.2010.02.017

« Previous Next »Respiratory Medicine
Volume 104, Issue 7 , Pages 995-1004, July 2010

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

J.A. van Noord
- Department of Respiratory Diseases, Atrium medisch centrum, Henri Dunantstraat 5, 6419 PC Heerlen, The Netherlands
- Corresponding author.
J.-L. Aumann
- Department of Respiratory Diseases, Virga Jesse Ziekenhuis, Stadsomvaart 11, 3500 Hasselt, Belgium
E. Janssens
- Department of Respiratory Diseases, Ziekenhuis Oost-Limburg, Bessemerstraat 478, 3620 Lanaken, Belgium
J.J. Smeets
- Department of Respiratory Diseases, Atrium medisch centrum, Henri Dunantstraat 5, 6419 PC Heerlen, The Netherlands
J. Zaagsma
- Department of Molecular Pharmacology, University Centre for Pharmacy, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands
A. Mueller
- Department of Clinical Research, Boehringer Ingelheim bv, Comeniusstraat 6, 1817 MS Alkmaar, The Netherlands
P.J.G. Cornelissen
- Department of Clinical Research, Boehringer Ingelheim bv, Comeniusstraat 6, 1817 MS Alkmaar, The Netherlands

Received 29 December 2009; accepted 21 February 2010. published online 19 March 2010.

Summary

Background

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 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.

Results

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.

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.

Keywords: Chronic obstructive pulmonary disease, Combination therapy, Inhaled long-acting anticholinergic, Inhaled long-acting β₂-agonist, Lung function, Dyspnea