Effects of Tiotropium on Exacerbations in Patients with COPD with Low or High Risk of Exacerbations: A Post-Hoc Analysis from the 4-Year UPLIFT® Trial.

A history of past exacerbations is a predictor of future events for patients with chronic obstructive pulmonary disease (COPD). Very little is known about the effect of pharmacologic therapies on patients with frequent or infrequent exacerbations. We conducted a post-hoc analysis of the Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT)trial database. Patients were classified as having a low risk of exacerbations if they experienced ≤1 exacerbation and no COPD-related hospitalization(s) in the year preceding trial entry or as high risk of exacerbations if they had ≥2 exacerbations (courses of oral steroids/antibiotics) or ≥1 COPD-related hospitalization(s) in the year preceding the trial. In patients at low risk or high risk for exacerbations, compared to placebo, tiotropium significantly reduced: 1) the time to first COPD exacerbation (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.74, 0.88; <0.0001; HR: 0.89; 95% CI: 0.81, 0.97; =0.0066, respectively); 2) the number of COPD exacerbations (rate ratio [RR]: 0.79; 95% CI: 0.72, 0.86; <0.0001; RR: 0.88; 95% CI: 0.81; 0.95; =0.0009). Furthermore, upon treatment with tiotropium, the proportion of patients transitioning from the low- to the high-risk exacerbations group was statistically lower compared to placebo (RR: 0.78; 95% CI: 0.67, 0.92; =0.0030) : This analysis shows that tiotropium reduces the risk of subsequent exacerbation and also prolongs time to first exacerbation, in both the high- and low-risk exacerbator subgroups. It also decreases the proportion of patients who shift from the low- to the high-risk exacerbations group compared to placebo.