ArticlesEffect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): a prespecified subgroup analysis of a randomised controlled trial
Introduction
The introduction of longacting β2 agonists,1 inhaled steroids,1, 2, 3, 4, 5 fixed combination products,1, 6, 7, 8 and a longacting anticholinergic drug9, 10, 11, 12 has substantially improved treatment of patients with chronic obstructive pulmonary disease (COPD). These agents improve pulmonary function and quality of life, and reduce the frequency of exacerbations.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 Reduction of exacerbations is especially important because they can accelerate the progression of the disease.13, 14 There are also data to suggest that treatment with a longacting anticholinergic drug12 and a combination product6 might reduce mortality. Additionally, treatment with a longacting anticholinergic drug was shown to reduce cardiovascular morbidity12 and incidence of respiratory failure.12 Most of these studies, however (apart from some that investigated inhaled corticosteroids2, 3, 4), mainly included patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III and IV disease (mean forced expiratory volume in 1 s [FEV1] ranging from 36% to 45% of predicted value). By contrast, little is known about treatment of COPD at earlier stages, such as GOLD stage II (moderate disease).
One fairly small (n=224) and short-term study showed that in patients with GOLD stage II COPD who were recruited in general practice, treatment with tiotropium improved FEV1 and forced vital capacity (FVC) compared with placebo.15 Another recent study showed that exercise limitation and dyspnoea were present in patients with GOLD stage I disease.16 Studies on activity measurement have consistently shown inactivity early in the disease (ie, GOLD stage I and II).17, 18, 19 Since comorbidities also start early in COPD, there is a case for earlier treatment.20 However, there is currently no clear evidence of the benefit of earlier treatment of COPD, although a recent study suggested that dyspnoea and hyperinflation during exercise could be improved in patients with symptomatic stage I disease with inhaled ipratropium.21
We investigated the effect of long-term treatment with tiotropium on outcomes in patients with GOLD stage II COPD, by use of data from the recently published Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial.12 The UPLIFT trial provided us with the largest group of patients with GOLD stage II disease treated with a longacting anticholinergic drug in a randomised placebo-controlled study.
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Patients
The design and main results of the UPLIFT trial have been reported elsewhere.12, 22 Briefly, the study was a 4-year, randomised, double-blind, placebo-controlled, parallel-group study in patients with moderate to severe COPD. Patients with a clear diagnosis of COPD, including a differential diagnosis with asthma, were eligible for inclusion. Eligibility criteria also included an age of 40 years or more, a smoking history of 10 pack-years or more, a postbronchodilator FEV1 of 70% or less of the
Results
Of 5993 randomised patients, 2739 (46%) had GOLD stage II COPD (figure 1). A higher proportion of patients in the control group (35%) discontinued study treatment than did patients in the tiotropium group (31%; p=0·024). Table 1 shows the baseline characteristics of study participants in the tiotropium and control groups by disease stage. The most relevant concomitant drugs used by patients with GOLD stage II disease at baseline and during the study are shown in table 2.
In the tiotropium group,
Discussion
This subgroup analysis of the UPLIFT trial showed that in patients with GOLD stage II COPD, tiotropium seemed to reduce the rate of decline of postbronchodilator FEV1 and the risk of exacerbations. Additionally, lung function and health-related quality of life were better in the tiotropium group than in the control group throughout the trial. Our findings suggest that treatment with a longacting anticholinergic drug has substantial benefits in patients with moderate COPD, and therefore provide
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2021, Chronic Diseases and Translational MedicineCitation Excerpt :Compared with GOLD stage III or IV, the UPLIFT study revealed that tiotropium bromide can reduce the annual lung function decline rate and improve the symptoms of COPD patients in GOLD stage II.12,84 Furthermore, in the tiotropium bromide group, the time to the first acute exacerbation and the time to hospitalization caused by acute exacerbation were extended, and the acute exacerbation risk was reduced.12 The Mesure de l’Influence de Spiriva1 sur les Troubles Respiratoires Aigus a Long terme (MISTRAL) study showed that in the subgroup of patients with moderate COPD with FEV1 ≥ 50%, the frequency of exacerbations in the tiotropium bromide group was lower than that in the placebo group (1.21 vs. 1.97, P < 0.01).93
Trajectories of COPD
2021, Encyclopedia of Respiratory Medicine, Second Edition
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