A 4-Year Trial of Tiotropium in Chronic Obstructive Pulmonary Disease

doi:10.1056/NEJMoa0805800

Volume 359:1543-1554		October 9, 2008		Number 15

A 4-Year Trial of Tiotropium in Chronic Obstructive Pulmonary Disease

Donald P. Tashkin, M.D., Bartolome Celli, M.D., Stephen Senn, Ph.D., Deborah Burkhart, B.S.N., Steven Kesten, M.D., Shailendra Menjoge, Ph.D., Marc Decramer, M.D., Ph.D., for the UPLIFT Study Investigators

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by Reilly, J. J.

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ABSTRACT

Background Previous studies showing that tiotropium improvesmultiple end points in patients with chronic obstructive pulmonarydisease (COPD) led us to examine the long-term effects of tiotropiumtherapy.

Methods In this randomized, double-blind trial, we compared4 years of therapy with either tiotropium or placebo in patientswith COPD who were permitted to use all respiratory medicationsexcept inhaled anticholinergic drugs. The patients were at least40 years of age, with a forced expiratory volume in 1 second(FEV₁) of 70% or less after bronchodilation and a ratio of FEV₁to forced vital capacity (FVC) of 70% or less. Coprimary endpoints were the rate of decline in the mean FEV₁ before andafter bronchodilation beginning on day 30. Secondary end pointsincluded measures of FVC, changes in response on St. George'sRespiratory Questionnaire (SGRQ), exacerbations of COPD, andmortality.

Results Of a total of 5993 patients (mean age, 65±8 years)with a mean FEV₁ of 1.32±0.44 liters after bronchodilation(48% of predicted value), we randomly assigned 2987 to the tiotropiumgroup and 3006 to the placebo group. Mean absolute improvementsin FEV₁ in the tiotropium group were maintained throughout thetrial (ranging from 87 to 103 ml before bronchodilation andfrom 47 to 65 ml after bronchodilation), as compared with theplacebo group (P<0.001). After day 30, the differences betweenthe two groups in the rate of decline in the mean FEV₁ beforeand after bronchodilation were not significant. The mean absolutetotal score on the SGRQ was improved (lower) in the tiotropiumgroup, as compared with the placebo group, at each time pointthroughout the 4-year period (ranging from 2.3 to 3.3 units,P<0.001). At 4 years and 30 days, tiotropium was associatedwith a reduction in the risks of exacerbations, related hospitalizations,and respiratory failure.

Conclusions In patients with COPD, therapy with tiotropium wasassociated with improvements in lung function, quality of life,and exacerbations during a 4-year period but did not significantlyreduce the rate of decline in FEV₁. (ClinicalTrials.gov number,NCT00144339 [ClinicalTrials.gov] .)

Source Information

From the David Geffen School of Medicine at the University of California, Los Angeles (D.P.T.); Caritas St. Elizabeth's Medical Center, Boston (B.C.); Glasgow University, Glasgow, Scotland (S.S.); Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (D.B., S.K., S.M.); and the University of Leuven, Leuven, Belgium (M.D.).

This article (10.1056/NEJMoa0805800) was published at www.nejm.org on October 5, 2008.

Address reprint requests to Dr. Tashkin at the David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Ave., Los Angeles, CA 90095-1690, or at dtashkin{at}mednet.ucla.edu.

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Related Letters:

Tiotropium in Chronic Obstructive Pulmonary Disease
Pedone C., Incalzi R. A., Chang E.-T., O'Connor A. B., Singh S., Furberg C. D., Loke Y. K., Sierra-Sánchez J. F., Alegre-del Rey E. J., Cobo I., Tashkin D. P., the UPLIFT Joint Advisory Committee
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N Engl J Med 2009; 360:185-187, Jan 8, 2009. Correspondence

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