Published ahead of print on October 4, 2007, doi:10.1164/rccm.200707-973OC
American Journal of Respiratory and Critical Care Medicine Vol 177. pp. 19-26, (2008)
© 2008 American Thoracic Society
doi: 10.1164/rccm.200707-973OC
The Prevention of Chronic Obstructive Pulmonary Disease Exacerbations by Salmeterol/Fluticasone Propionate or Tiotropium Bromide
Jadwiga A. Wedzicha1,
Peter M. A. Calverley2,
Terence A. Seemungal3,
Gerry Hagan4,
Zainab Ansari4 and
Robert A. Stockley5 for the INSPIRE Investigators
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 Sciences, The University of the West Indies, Mt. Hope, Trinidad and Tobago; 4 Respiratory Medicines Centre, GlaxoSmithKline, Greenford, Middlesex, United Kingdom; and 5 Department of Medicine, University Hospital Birmingham, NHS Foundation Trust, Birmingham, United Kingdom
Correspondence and requests for reprints should be addressed to Jadwiga A. Wedzicha, M.D., Royal Free & University College Medical School, Rowland Hill Street, Hampstead, London, UK. 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/antiinflammatory combination (salmeterol/fluticasone propionate) 50/500 µg twice daily and the long-acting bronchodilator (tiotropium) 18 µg once daily in preventing exacerbations and related outcomes in severe and very severe COPD.
Methods: A total of 1,323 patients (mean age, 64 yr, post-bronchodilator FEV1, 39% predicted) were randomized in this 2-year, double-blind, double-dummy parallel study.
Measurements and Main Results: Primary endpoint was health care utilization exacerbation rate. Other endpoints included health status measured by St. George's 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 modeled annual exacerbation rate was 1.28 in the salmeterol/fluticasone propionate group and 1.32 in the tiotropium group (rate ratio, 0.967; 95% confidence interval [CI], 0.836–1.119]; 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, 0.1–4.0; P = 0.038). Mortality was significantly lower in the salmeterol/fluticasone propionate group; 21 (3%) of patients in this group died compared with 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 while 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 registered with www.clinicaltrials.gov (NCT 00361959).
Key Words: chronic obstructive pulmonary disease • exacerbations • mortality • health status
| AT A GLANCE COMMENTARY
Scientific Knowledge on the Subject
A variety of treatments, including salmeterol, tiotropium, and inhaled corticosteroids have been shown to prevent COPD exacerbations. However, the efficacy of a combination of inhaled corticosteroids with salmeterol versus tiotropium has not been tested.
What This Study Adds to the Field
The study shows no difference in reduction of exacerbations between salmeterol/fluticasone propionate and tiotropium, although patients receiving the salmeterol/fluticasone combination were less likely to withdraw, had better health status, and had better survival.
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Copyright © 2008 American Thoracic Society
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