Tiotropium in Patients With Airflow Limitation According to the Fixed Ratio But Not the Lower Limit of Normal: A Secondary Analysis of the Tiotropium in Early-COPD Study.

Abstract

Background: Patients with airflow limitation according to the fixed ratio but not the lower limit of normal (LLN) (FR+LLN-) have a poorer respiratory prognosis and higher mortality than the normal fixed ratio. However, whether tiotropium treatment improves respiratory health outcomes in patients with FR+LLN- remains unclear.

Methods: This was a secondary analysis of the 24-month Tie-COPD study, a multicentre, randomized, double-blind clinical trial comparing tiotropium with placebo for mild-to-moderate COPD. FR+LLN- was defined as a post-bronchodilator FEV₁/FVC ratio of <0.70 but ≥LLN. The primary endpoint was the between-group difference in the change from baseline to 24 months in pre-bronchodilator FEV₁. Key secondary endpoints included the between-group difference in the annual decline in pre-bronchodilator FEV₁ and exacerbations.

Results: In the Tie-COPD study, 92 patients (12%) had FR+LLN-. Tiotropium resulted in a significantly higher pre-bronchodilator FEV₁ at 24 months (difference, 191 mL; 95% confidence interval [CI] 99, 283), with a least-squares mean (LSM) change from baseline of 47 mL (95% CI -13, 108) versus -140 mL (95% CI -215, -64) with placebo. The annual decline in the pre-bronchodilator FEV₁ was 24 mL/year with tiotropium and 89 mL/year with placebo (difference 60 mL/year; 95% CI 2, 118) from 30 days through 24 months. Tiotropium reduced total exacerbations compared with placebo (relative risk=0.50; 95% CI 0.27, 0.94).

Conclusion: This study demonstrated tiotropium treatment improved lung function, ameliorated lung function decline, and reduced exacerbations compared with placebo in patients with FR+LLN-, providing evidence-based medicine evidence for the treatment in this population.