Mortality in the 4-year trial of tiotropium (UPLIFT) in patients with chronic obstructive pulmonary disease.
BACKGROUND
In the 4-year UPLIFT trial, tiotropium improved lung function and health-related quality of life and decreased exacerbations compared with usual respiratory medications except inhaled anticholinergics in patients with chronic obstructive pulmonary disease (COPD). Mortality and its causes was a secondary endpoint in UPLIFT.


OBJECTIVE
We describe the effect of tiotropium on survival and analyze differences between mortality during treatment and during follow-up of discontinued patients.


METHODS
This study involved a randomized, double-blind trial comparing tiotropium with placebo in patients with COPD (>or=40 yr of age; postbronchodilator FEV(1) <or=70%; FEV(1)/FVC <or=70%). Mortality was evaluated during treatment and with follow-up of discontinued patients. Cause of death was adjudicated by an endpoint committee.


RESULTS
A total of 5,993 patients were randomized, 3,006 to placebo and 2,987 to tiotropium. While patients were receiving treatment, there were 792 deaths, with a lower risk in the tiotropium group (hazard ratio, 0.84; 95% confidence interval [CI], 0.73-0.97). Statistical significance was observed at the end of the protocol-defined treatment period (P = 0.034) but not 30 days thereafter (P = 0.086). Adjustment by GOLD stage, sex, age, baseline smoking behavior, and baseline respiratory medications subgroups did not alter the results of the analysis. The most common causes of death adjudicated by an independent end-point committee were lower respiratory, cancer, general disorders, and cardiac disorders. The hazard ratios for lower respiratory and cardiac mortality during treatment were 0.86 (95% CI, 0.68-1.09) and 0.86 (95% CI, 0.75-0.99), respectively.


CONCLUSIONS
Treatment with tiotropium over 4 years is associated with decreased mortality, with the effect being most prominent in the cardiac and respiratory systems.
Celli
Bartolome
B
Brigham and Women's Hospital and St. Elizabeth's Medical Center, Boston, MA 02115, USA. bcelli@copdnet.org
Decramer
Marc
M
Kesten
Steven
S
Liu
Dacheng
D
Mehra
Sunil
S
Tashkin
Donald P
DP
D000368:Aged; D002423:Cause of Death; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality*; D011788:Quality of Life; D012602:Scopolamine Derivatives / Q000008:administration & dosage / Q000627:therapeutic use*; D012907:Smoking; D000069447:Tiotropium Bromide
D018680:Cholinergic Antagonists; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide