The beneficial effects of pharmacotherapy for chronic obstructive pulmonary disease
(COPD) are well established. However, there are few data for treatment in the early
stages of the disease. We examined the effect of tiotropium on outcomes in a large
subgroup of patients with moderate COPD.
The Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT)
study was a randomised, double-blind, placebo-controlled trial undertaken in 487 centres
in 37 countries. 5993 patients aged 40 years or more with COPD were randomly assigned
to receive 4 years of treatment with either once daily tiotropium (18 microg; n=2987)
or matching placebo (n=3006), delivered by an inhalation device. Randomisation was
by computer-generated blocks of four, with stratification according to study site.
In a prespecified subgroup analysis, we investigated the effects of tiotropium in
patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage
II disease. Primary endpoints were the yearly rates of decline in prebronchodilator
forced expiratory volume in 1 s (FEV(1)) and in postbronchodilator FEV(1), beginning
on day 30 until completion of double-blind treatment. The analysis included all patients
who had at least three measurements of pulmonary function. This study is registered
with ClinicalTrials.gov, number NCT00144339.
2739 participants (mean age 64 years [SD 9]) had GOLD stage II disease at randomisation
(tiotropium, n=1384; control, n=1355), with a mean postbronchodilator FEV(1) of 1.63
L (SD 0.37; 59% of predicted value). 1218 patients in the tiotropium group and 1157
in the control group had three or more measurements of postbronchodilator pulmonary
function after day 30 and were included in the analysis. The rate of decline of mean
postbronchodilator FEV(1) was lower in the tiotropium group than in the control group
(43 mL per year [SE 2] vs 49 mL per year [SE 2], p=0.024). For prebronchodilator pulmonary
function, 1221 patients in the tiotropium group and 1158 in the control group had
three or more measurements and were included in the analysis. The rate of decline
of mean prebronchodilator FEV(1) did not differ between groups (35 mL per year [SE
2] vs 37 mL per year [SE 2]; p=0.38). Health status, measured with the St George's
Respiratory Questionnaire, was better at all timepoints in the tiotropium group than
in the control group (p</=0.006 for all timepoints). Time to first exacerbation and
time to exacerbation resulting in hospital admission were also longer in the tiotropium
group than in the control group (hazard ratio 0.82, 95% CI 0.75-0.90, and 0.74, 0.62-0.88,
Tiotropium seemed to reduce the rate of decline of postbronchodilator FEV(1) in patients
with GOLD stage II COPD. This finding and the other improvements in outcomes suggest
that treatment of COPD should begin at an early stage of the disease.
Boehringer Ingelheim and Pfizer Pharmaceuticals.