{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T19:18:22Z","timestamp":1778786302342,"version":"3.51.4"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2008,1,1]],"date-time":"2008-01-01T00:00:00Z","timestamp":1199145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Exacerbations are key drivers of morbidity and mortality in chronic obstructive pulmonary disease (COPD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We compared the relative efficacy of the long-acting inhaled bronchodilator\/antiinflammatory combination (salmeterol\/fluticasone propionate) 50\/500 \u03bcg twice daily and the long-acting bronchodilator (tiotropium) 18 \u03bcg once daily in preventing exacerbations and related outcomes in severe and very severe COPD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>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\u20131.119]; 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\u20134.0; 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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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\u2013treated patients.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT00361959).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.200707-973oc","type":"journal-article","created":{"date-parts":[[2007,10,4]],"date-time":"2007-10-04T21:20:42Z","timestamp":1191532842000},"page":"19-26","source":"Crossref","is-referenced-by-count":592,"title":["The Prevention of Chronic Obstructive Pulmonary Disease Exacerbations by Salmeterol\/Fluticasone Propionate or Tiotropium Bromide"],"prefix":"10.1093","volume":"177","author":[{"given":"Jadwiga A.","family":"Wedzicha","sequence":"first","affiliation":[{"name":"Academic Unit of Respiratory Medicine, Royal Free and University College Medical School, University College London, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter M. 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Hope, Trinidad and Tobago"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerry","family":"Hagan","sequence":"additional","affiliation":[{"name":"Respiratory Medicines Centre, GlaxoSmithKline, Greenford, Middlesex, United Kingdom; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zainab","family":"Ansari","sequence":"additional","affiliation":[{"name":"Respiratory Medicines Centre, GlaxoSmithKline, Greenford, Middlesex, United Kingdom; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Stockley","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Hospital Birmingham, NHS Foundation Trust, Birmingham, United 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