The online version of this article (doi:10.1186/1465-9921-15-64) contains supplementary material, which is available to authorized users.
In the past 5 years, Pierre-Régis Burgel has received fees for speaking, organising education or research, or consulting from Almirall, Nycomed-Takeda, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Pfizer. Jean-Louis Paillasseur was full time employee of Clindatafirst and EFFI-STAT, CROs which received fees from Boehringer Ingelheim, Nycomed and AstraZeneca. Daniel Dusser has received fees for speaking, organising education or research, or consulting from Boehringer Ingelheim, Novartis, Pfizer, Chiesi, Dey Pharma and Nycomed. Nicolas Roche has received (i) fees for speaking, organising education or research, or consulting from Aerocrine, Almirall, Altana Pharma-Nycomed-Takeda, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, MEDA, MSD-Chibret, Mundipharma, Novartis, Pfizer, Stallergenes, TEVA; (ii) research grants from Novartis, Nycomed, Boehringer Ingelheim and Pfizer. Yufeng Liu has received consulting fees from Boehringer-Ingelheim. Marc Decramer has received research grants or fees for consulting or speaking from Novartis, Nycomed, Boehringer Ingelheim, GlaxoSmithKline, Altana and AstraZeneca. Dacheng Liu, Armin Furtwaengler, and Norbert Metzdorf are full-time employees of Boehringer Ingelheim Pharma GmbH & Co KG.
PRB, JLP, DD, NR, and MD conceived and designed the paper; DL and YL performed the statistical analysis; PRB, JLP, DD, NR, AF, NM, and MD performed the analysis and interpretation. PRB, JLP, DD, NR, and MD helped to draft the manuscript for important intellectual content. All authors read and approved the final manuscript.
Inhaled therapies reduce risk of chronic obstructive pulmonary disease (COPD) exacerbations, but their effect on mortality is less well established. We hypothesized that heterogeneity in baseline mortality risk influenced the results of drug trials assessing mortality in COPD.
The 5706 patients with COPD from the Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) study that had complete clinical information for variables associated with mortality (age, forced expiratory volume in 1 s, St George’s Respiratory Questionnaire, pack-years and body mass index) were classified by cluster analysis. Baseline risk of mortality between clusters, and impact of tiotropium were evaluated during the 4-yr follow up.
Four clusters were identified, including low-risk (low mortality rate) patients (n = 2339; 41%; cluster 2), and high-risk patients (n = 1022; 18%; cluster 3), who had a 2.6- and a six-fold increase in all-cause and respiratory mortality compared with cluster 2, respectively. Tiotropium reduced exacerbations in all clusters, and reduced hospitalizations in high-risk patients (p < 0.05). The beneficial effect of tiotropium on all-cause mortality in the overall population (hazard ratio, 0.87; 95% confidence interval, 0.75–1.00, p = 0.054) was explained by a 21% reduction in cluster 3 (p = 0.07), with no effect in other clusters.
Large variations in baseline risks of mortality existed among patients in the UPLIFT® study. Inclusion of numerous low-risk patients may have reduced the ability to show beneficial effect on mortality. Future clinical trials should consider selective inclusion of high-risk patients.
Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013, 187: 347-365. 10.1164/rccm.201204-0596PP. PubMedCrossRef
Burgel PR, Paillasseur JL, Dusser D, Roche N, Liu D, Liu Y, Furtwaengler A, Metzdorf N, Decramer M: Variations in mortality risk among COPD patients in clinical trials: Data from the UPLIFT study [abstract]. Am J Respir Crit Care Med. 2013, 187: A5558-
Puhan MA, Garcia-Aymerich J, Frey M, ter RG, Anto JM, Agusti AG, Gomez FP, Rodriguez-Roisin R, Moons KG, Kessels AG, et al: Expansion of the prognostic assessment of patients with chronic obstructive pulmonary disease: the updated BODE index and the ADO index. Lancet. 2009, 374: 704-711. 10.1016/S0140-6736(09)61301-5. PubMedCrossRef
Domingo-Salvany A, Lamarca R, Ferrer M, Garcia-Aymerich J, Alonso J, Felez M, Khalaf A, Marrades RM, Monso E, Serra-Batlles J, Anto JM: Health-related quality of life and mortality in male patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2002, 166: 680-685. 10.1164/rccm.2112043. PubMedCrossRef
Webinar draft GFI on enrichment strategies for clinical trials to support approval of human drugs and biological products. http://www.fda.gov/Drugs/ucm343578.htm,
- Tiotropium might improve survival in subjects with COPD at high risk of mortality
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II