Impact of tiotropium on the course of moderate-to-very severe chronic obstructive pulmonary disease: the UPLIFT^® trial

Abstract

The Understanding Potential Long-term Improvements in Function with Tiotropium (UPLIFT^®) trial was a global 4-year randomized placebo-controlled clinical trial that evaluated the long-term impact of tiotropium bromide 18 µg once daily on the accelerated age-related decline in pre- and post-bronchodilator forced expiratory volume in 1 s (FEV₁; co-primary end points). Secondary end points included lung function at serial clinic visits, health-related quality of life, exacerbations, exacerbation-related hospitalizations, mortality, safety and tolerability. The study was carried out in 5992 patients (75% male, mean age 65 years, 30% current smokers) with moderate-to-very severe chronic obstructive pulmonary disease who were permitted to receive prescribed treatment with long-acting β₂-agonists and/or inhaled corticosteroids in addition to the study drug. While the results failed to show an effect of tiotropium on the primary end points (rate of decline in pre- and post-bronchodilator FEV₁), they did show improvements in lung function and health-related quality of life that were maintained throughout the study and a reduction in the risk of exacerbations and related hospitalizations. Tiotropium also reduced all-cause mortality in patients on treatment over the 4-year trial period and reduced lower respiratory and cardiovascular morbidity, including respiratory failure and myocardial infarction. Adverse events were consistent with the drug’s known anticholinergic pharmacology.

Keywords::

• chronic obstructive pulmonary disease
• COPD
• LAMA
• long-acting anticholinergic
• long-acting antimuscarinic
• tiotropium
• UPLIFT

Financial & competing interests disclosure

Donald P Tashkin received fees for serving on consulting/advisory boards from Boehringer Ingelheim, AstraZeneca, Dey Laboratories and Schering-Plough; speaker fees from Boehringer Ingelheim, Pfizer, Dey Laboratories and GlaxoSmithKline; and grant support from Almirall, Boehringer Ingelheim, Dey Laboratories, GlaxoSmithKline, Pfizer, Novartis and Sepracor. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.