Limits...
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.

Show MeSH

Related in: MedlinePlus

Kaplan-Meier plots of exacerbations. Time to first exacerbation (A) and severe exacerbation (B) by cluster in the control group (n = 2862 patients) are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Kaplan-Meier plots of exacerbations. Time to first exacerbation (A) and severe exacerbation (B) by cluster in the control group (n = 2862 patients) are shown.

Mentions: The total number of deaths in the control group was 463 (16.1%). All-cause mortality rates were markedly different among clusters ranging from 11.1% in cluster 2 to 26.1% in cluster 3 (Table 2). Deaths related to respiratory causes occurred in 158 (5.5%) patients. Respiratory mortality was very low in cluster 2 (2.1%) and very high in cluster 3 (12.7%). Kaplan-Meier analyses of all-cause mortality and respiratory mortality by cluster are presented in Figure 2. Cox regression showed significant difference among clusters (p < 0.0001).Risk of exacerbations and severe exacerbations were markedly different among clusters. Patients in cluster 3 had the highest rates of exacerbations (1.21 ± 0.06 per patient/year) and hospitalizations (0.33 ± 0.03 per patient/year), whereas patients in cluster 2 had the lowest rates of exacerbations (0.69 ± 0.03 per patient/year) and hospitalizations (0.11 ± 0.01 per patient/year). Kaplan-Meier analyses of time to first exacerbation and to first severe exacerbation by cluster in the control group are presented in Figure 3. Cox regression showed significant difference among clusters (p < 0.0001).Cox analyses comparing baseline risks of exacerbations, severe exacerbations, all-cause and respiratory mortality by clusters in the control group are shown in Figure 4.


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)

Kaplan-Meier plots of exacerbations. Time to first exacerbation (A) and severe exacerbation (B) by cluster in the control group (n = 2862 patients) are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Kaplan-Meier plots of exacerbations. Time to first exacerbation (A) and severe exacerbation (B) by cluster in the control group (n = 2862 patients) are shown.
Mentions: The total number of deaths in the control group was 463 (16.1%). All-cause mortality rates were markedly different among clusters ranging from 11.1% in cluster 2 to 26.1% in cluster 3 (Table 2). Deaths related to respiratory causes occurred in 158 (5.5%) patients. Respiratory mortality was very low in cluster 2 (2.1%) and very high in cluster 3 (12.7%). Kaplan-Meier analyses of all-cause mortality and respiratory mortality by cluster are presented in Figure 2. Cox regression showed significant difference among clusters (p < 0.0001).Risk of exacerbations and severe exacerbations were markedly different among clusters. Patients in cluster 3 had the highest rates of exacerbations (1.21 ± 0.06 per patient/year) and hospitalizations (0.33 ± 0.03 per patient/year), whereas patients in cluster 2 had the lowest rates of exacerbations (0.69 ± 0.03 per patient/year) and hospitalizations (0.11 ± 0.01 per patient/year). Kaplan-Meier analyses of time to first exacerbation and to first severe exacerbation by cluster in the control group are presented in Figure 3. Cox regression showed significant difference among clusters (p < 0.0001).Cox analyses comparing baseline risks of exacerbations, severe exacerbations, all-cause and respiratory mortality by clusters in the control group are shown in Figure 4.

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