1. Patients with mild or moderate COPD (chronic obstructive pulmonary disease) randomized to receive tiotropium had a significantly higher FEV1 (forced expiratory volume in 1 second) after bronchodilator use at 24 months since starting treatment than those who received a placebo inhaler.
2. Those who received daily inhaled tiotropium experienced a significantly decreased frequency of acute COPD exacerbations.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Chronic obstructive pulmonary disease is an increasingly prevalent and highly morbid condition with far-reaching worldwide penetration. Little is known about the treatment of early-stage COPD, defined as GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages 1 and 2. In this randomized controlled study, participants with GOLD stage 1 or 2 COPD were randomized to receive either daily tiotropium or a placebo inhaler and were followed for 24 months to assess for changes in FEV1 and other measures of respiratory function. After 24 months, the authors found a significantly improved FEV1 in patients who received tiotropium compared to placebo. This corresponded with a significant improvement in the annual decline in FEV1 after bronchodilator use in the tiotropium group compared to placebo, though a significant finding was not found for the annual decline in FEV1 before bronchodilator use. Importantly, use of tiotropium was also linked with a significantly decreased frequency of acute exacerbations of COPD compared to placebo. Those in the tiotropium arm experienced significantly higher rates of oropharyngeal discomfort and dry mouth than the placebo group, but other adverse events were similar between groups.
This trial provides supportive evidence for the treatment of GOLD stage 1 and 2 COPD with tiotropium inhalers. It draws strength from its randomized controlled design. A drawback includes high withdrawal from both the treatment and placebo groups. Furthermore, given the relatively mild form of COPD experienced by trial participants, medication adherence to a daily inhaler may be difficult in a real-world population.
Relevant Reading: A 4-year trial of tiotropium in chronic obstructive pulmonary disease
In-Depth [randomized controlled trial]: Study participants were between 40 and 85 years old and were diagnosed with COPD of GOLD stage 1 or 2, defined as an FEV1:FVC ratio of less than 0.70 after bronchodilator use plus respiratory symptoms, a history of exposure to risk factors (such as smoking or air pollution), or both and an FEV1 of 50% or more of the predicted value after albuterol inhalation. Key exclusion criteria included patients with a COPD exacerbation in the preceding 4 weeks to enrollment, large-airway disease, cancer, asthma, or severe systemic disease. Subjects were randomized to receive either tiotropium 18 mcg once daily or a matching placebo. Of the 841 patients enrolled, 771 (n = 383 for placebo, n = 388 for tiotropium) were included in the full analysis set (others did not receive spirometry data). Spirometric values were measured at screening, and at visits during months 1, 6, 12, 18, 24, and 25. The groups were well matched across a number of variables and in general involved a mostly male population with an age in the mid 60’s, approximately 40% of whom were current smokers. Those randomized to the tiotropium group had a significantly higher FEV1 before bronchodilator use than those in the placebo group at month 24 (between-group difference of 157mL, 95% CI, 123 to 192; p < 0.001). The annual decline in the FEV1 before bronchodilator use approached significance for the tiotropium group (difference 15mL per year; 95% CI, -1 to 31; p = 0.06), whereas there was a significantly lower rate of decline in the FEV1 after bronchodilator use in the tiotropium group (difference, 22 mL per year; 95% CI, 6 to 37, p = 0.006) compared to the placebo group. There were significantly fewer acute exacerbations of COPD in the tiotropium group than the placebo group (0.27 vs. 0.50 events per patient-year; risk ratio 0.53; 95% CI, 0.39 to 0.73; p < 0.001). Oropharyngeal discomfort or dry mouth was experienced by 63 patients in the tiotropium group (15%) versus 28 (6.6%) in the placebo group.
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