UCLA

Background: Disease progression in chronic obstructive pulmonary disease (COPD) is associated with decline in exercise performance over time. We assessed whether tiotropium might mitigate this by determining its effect on treadmill endurance time (ET) over 2 years.

Methods: Randomized, double-blind, placebo-controlled trial of tiotropium 18 µg daily in patients with COPD (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 70%; postbronchodilator FEV1 < 65%). Primary endpoint: ET at 90% of baseline maximum work rate at 96 weeks. Secondary endpoints: ET at other visits, ET by smoking status, spirometry, St George Respiratory Questionnaire (SGRQ).

Results: 519 patients randomized (tiotropium 260, placebo 259), mean 65 years, 77% men, 34% continuing smokers, FEV1 1.25 L (44% predicted). Significantly more patients discontinued placebo: hazard ratio (95% CI) 0.61 (0.44, 0.83). Baseline ET was 301 s (improvement tiotropium/placebo: 13% overall, P = 0.009; 18% at 48 weeks, P = 0.004; 13% at 96 weeks, P = 0.106). In patients with baseline ET between 2-10 minutes (n = 404), improvement at 96 weeks was 19% (P = 0.04). Current smokers had higher ET with tiotropium vs placebo (P = 0.018). FEV1/FVC improved with tiotropium (P < 0.01). SGRQ total score at 96 weeks improved with tiotropium versus placebo by 4.03 units (P = 0.007).

Conclusions: Treadmill ET was numerically greater over 2 years with tiotropium versus placebo. However, 96-week difference was not statistically significant. Spirometry and health status also improved with tiotropium over 2 years, attesting to the benefits of long-acting bronchodilator therapy.