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Volume 104, Issue 7, Pages 995-1004 (July 2010)


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

J.A. van NoordaCorresponding Author Informationemail address, J.-L. Aumannb, E. Janssensc, J.J. Smeetsa, J. Zaagsmad, A. Muellere, P.J.G. Cornelissene

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.

a Department of Respiratory Diseases, Atrium medisch centrum, Henri Dunantstraat 5, 6419 PC Heerlen, The Netherlands

b Department of Respiratory Diseases, Virga Jesse Ziekenhuis, Stadsomvaart 11, 3500 Hasselt, Belgium

c Department of Respiratory Diseases, Ziekenhuis Oost-Limburg, Bessemerstraat 478, 3620 Lanaken, Belgium

d Department of Molecular Pharmacology, University Centre for Pharmacy, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands

e Department of Clinical Research, Boehringer Ingelheim bv, Comeniusstraat 6, 1817 MS Alkmaar, The Netherlands

Corresponding Author InformationCorresponding author.

 Study not registered in the Clinical Trials Registry; all patients were entered before implementation of the registry.

PII: S0954-6111(10)00087-9

doi:10.1016/j.rmed.2010.02.017


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