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Published ahead of print on October 4, 2007, doi:10.1164/rccm.200707-973OC

Am. J. Respir. Crit. Care Med., Volume 177, Number 1, January 2008, 19-26

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Submitted on July 2, 2007
Accepted on October 4, 2007

The Prevention of COPD Exacerbations by Salmeterol/Fluticasone Propionate or Tiotropium Bromide

Jadwiga A Wedzicha1*, Peter MA Calverley2, Terence A Seemungal3, Gerry Hagan4, Zainab Ansari4, and Robert A Stockley5

1 Academic Unit of Respiratory Medicine, Royal Free and University College Medical School, University College London, London, United Kingdom, 2 Department of Medicine, University Hospital Aintree, Liverpool, United Kingdom, 3 Department of Clinical Medical Scienes, The University of the West Indies, Mount Hope, Trinidad and Tobago, 4 Respiratory Medicines Centre, GSK, Greenford, Middlesex, United Kingdom, 5 Department of Medicine, University Hospital Birmingham NHS Foundation Trust, Birmingham, United Kingdom

* To whom correspondence should be addressed. E-mail: j.a.wedzicha{at}medsch.ucl.ac.uk.

Rationale: Exacerbations are key drivers of morbidity and mortality in chronic obstructive pulmonary disease (COPD). Objectives: We compared the relative efficacy of the long-acting inhaled bronchodilator/anti-inflammatory combination (salmeterol/fluticasone propionate) 50/500mcg bd and the long-acting bronchodilator (tiotropium) 18mcg od in preventing exacerbations and related outcomes in moderate-severe COPD. Methods: 1323 patients (mean age 64yr, forced expiratory volume in 1sec 39% predicted) were randomized in 2-year, double-blind, double-dummy, parallel study. Measurements and Main Results: Primary endpoint was healthcare utilization exacerbation rate. Other endpoints included health status measured by St. Georges Respiratory Questionnaire (SGRQ), mortality, adverse events and study withdrawal. Probability of withdrawing from the study was 29% greater with tiotropium than salmeterol/fluticasone propionate (p=0.005). The modelled annual exacerbation rate was 1.28 in the salmeterol/fluticasone propionate group and 1.32 in the tiotropium group (rate ratio 0.967 [95% CI: 0.836 to 1.119]; p=0.656). The SGRQ total score was statistically significantly lower at 2 years on salmeterol/fluticasone propionate versus tiotropium (difference 2.1 units, 95% CI: 0.1 to 4.0, p=0.038). Mortality was significantly lower in the salmeterol/fluticasone propionate group; 21 (3%) of patients in this group died compared to 38 (6%) in the tiotropium group (p=0.032). More pneumonias were reported in the salmeterol/fluticasone propionate group relative to tiotropium (p=0.008). Conclusions: We found no difference in exacerbation rate between salmeterol/fluticasone propionate and tiotropium. More patients failed to complete the study receiving tiotropium. A small statistically significant beneficial effect was found on health status, with an unexpected finding of lower deaths in salmeterol/fluticasone propionate treated patients. Clinical Trial Registry Information: ID# NCT00361959 registered at www.clinicaltrials.gov
Key words: COPD, exacerbations, mortality, health status




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