A team of international collaborators from France, Germany, Belgium, and the United States (University of North Carolina at Chapel Hill and Boehringer Ingelheim Pharma GmbH & Co KG) found benefits of tiotropium in patients with chronic obstructive pulmonary disease (COPD). While it was known inhaled therapies can reduce risk of exacerbations, the researchers were interested in the effects of treatment on mortality.
The present study is meaningful as a follow-up to Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT). Patients were not stratified during the study and were considered as a whole, which may have influenced the way the results of the clinical trial patients were interpreted.
Cluster analysis of the 5706 patients with COPD from UPLIFT was conducted, and the results were published in Respiratory Research, a journal from BioMed Central. There were four clusters generated from age, body mass index, post-bronchodilator forced expiratory volume in one second (FEV1), smoking, and SGRQ (St. George’s Respiratory Questionnaire) scores. Cluster 1 was GOLD Stage 2 or 3 patients with a relatively preserved health-related quality of life, despite heavy smoking and high rates of comorbidities. Cluster 2 was GOLD Stage 2 patients with moderate health-related quality of life impairment and low rates of comorbidities. Cluster 3 was GOLD Stage 3 and 4 patients with severe health-related quality of life impairment, high rates of comorbidities, and heavy tobacco use. Finally, Cluster 4 was similar to cluster 3, but patients had less severe airflow limitations, less severe health-related quality of life impairment, fewer comorbidities, and lower tobacco use.
Tiotropium significantly lessened the rate of hospitalization in high-risk patients and reduced exacerbations in all clusters. In the overall population, all-cause mortality was reduced by 21% in cluster 3 but no other cluster. Accordingly, the authors believe the impact of tiotropium may have been obscured by including low-risk patients in the UPLIFT study, as they made up 41% of the population. Therefore, they concluded, “Future clinical trials should consider selective inclusion of high-risk patients.”