Impact of tiotropium on the course of moderate-to-very severe chronic obstructive pulmonary disease: the UPLIFT trial.
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 microg once daily on the accelerated age-related decline in pre- and post-bronchodilator forced expiratory volume in 1 s (FEV(1); 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 beta(2)-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 FEV(1)), 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.
Tashkin
Donald P
DP
David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90272, USA. dtashkin@mednet.ucla.edu
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000368:Aged; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018680:Cholinergic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005541:Forced Expiratory Volume; D006760:Hospitalization; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D012602:Scopolamine Derivatives / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013997:Time Factors; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide