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Tiotropium might improve survival in subjects with COPD at high risk of mortality.

Burgel PR, Paillasseur JL, Dusser D, Roche N, Liu D, Liu Y, Furtwaengler A, Metzdorf N, Decramer M, UPLIFT® Study Investigato - Respir. Res. (2014)

Bottom Line: 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.Inclusion of numerous low-risk patients may have reduced the ability to show beneficial effect on mortality.

View Article: PubMed Central - HTML - PubMed

Affiliation: Hôpitaux Universitaires Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris, France. pierre-regis.burgel@cch.aphp.fr.

ABSTRACT

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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Dendrogram showing progressive joining of the clustering process. Data can be optimally grouped into four clusters. Characteristics of subjects in each cluster are presented in Table 1. The vertical line identifies the optimal number of clusters in the data.
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Figure 1: Dendrogram showing progressive joining of the clustering process. Data can be optimally grouped into four clusters. Characteristics of subjects in each cluster are presented in Table 1. The vertical line identifies the optimal number of clusters in the data.

Mentions: The present analysis is based on 5706 patients with COPD (95.2% of the randomized population) with complete data for age, BMI, post-bronchodilator FEV1 (percent predicted), SGRQ total score, and cumulative smoking (pack-years). Classification of these patients using cluster analysis resulted in a dendrogram that showed the progressive joining of the clustering process (Figure 1); patients could be optimally classified in four clusters (see Methods section).


Tiotropium might improve survival in subjects with COPD at high risk of mortality.

Burgel PR, Paillasseur JL, Dusser D, Roche N, Liu D, Liu Y, Furtwaengler A, Metzdorf N, Decramer M, UPLIFT® Study Investigato - Respir. Res. (2014)

Dendrogram showing progressive joining of the clustering process. Data can be optimally grouped into four clusters. Characteristics of subjects in each cluster are presented in Table 1. The vertical line identifies the optimal number of clusters in the data.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4061116&req=5

Figure 1: Dendrogram showing progressive joining of the clustering process. Data can be optimally grouped into four clusters. Characteristics of subjects in each cluster are presented in Table 1. The vertical line identifies the optimal number of clusters in the data.
Mentions: The present analysis is based on 5706 patients with COPD (95.2% of the randomized population) with complete data for age, BMI, post-bronchodilator FEV1 (percent predicted), SGRQ total score, and cumulative smoking (pack-years). Classification of these patients using cluster analysis resulted in a dendrogram that showed the progressive joining of the clustering process (Figure 1); patients could be optimally classified in four clusters (see Methods section).

Bottom Line: 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.Inclusion of numerous low-risk patients may have reduced the ability to show beneficial effect on mortality.

View Article: PubMed Central - HTML - PubMed

Affiliation: Hôpitaux Universitaires Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris, France. pierre-regis.burgel@cch.aphp.fr.

ABSTRACT

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Show MeSH
Related in: MedlinePlus