The functional impact of adding salmeterol and tiotropium in patients with stable COPD

Abstract

AbstractThe aim of this double-blind, double-dummy, crossover, randomised, pilot study was to explore the acute effects of adding salmeterol and tiotropium in patients with stable COPD. A total of 20 outpatients with stable COPD were enrolled. Single doses of 18-μg tiotropium, 50-μg salmeterol, and 18-μg tiotropium+50-μg salmeterol were given. Serial measurements of forced expiratory volume in 1s (FEV1) were performed over 24h. The mean maximum increases in FEV1 from pre-dosing value on each of the dosing days were 0.165l (95% CI: 0.098–0.232) for tiotropium, 0.241l (95% CI: 0.151–0.332) for salmeterol, and 0.290l (95% CI: 0.228–0.353) for the combination and occurred 4h after inhalation of tiotropium or salmeterol and 3h after the combination. At 12h, the mean increases in FEV1 from pre-dosing value were 0.071l (95% CI: 0.001–0.141; P=0.047) for tiotropium, 0.069l (95% CI: 0.018-0.120; P=0.010) for salmeterol, and 0.108l (95% CI: 0.047–0.170; P=0.001) for the tiotropium+salmeterol combination. Only the difference between salmeterol and tiotropium+salmeterol was statistically significant (P=0.009). At 24h, the mean FEV1 value was still higher than the mean pre-dosing value for tiotropium (0.042l; 95% CI: −0.012–0.097; P=0.119) and the tiotropium+salmeterol combination (0.051l; 95% CI: 0.015–0.087; P=0.007), but not for salmeterol alone (−0.013l; 95% CI: −0.041–0.014; P=0.324). The FEV1 area under the curve (AUCs0−12h) were 1.657l (95% CI: 1.152–2.162) for tiotropium, 2.068l (95% CI: 1.385–2.752) for salmeterol, and 2.541l (95% CI: 1.954–3.129) for tiotropium+salmeterol. Only the difference between tiotropium and the tiotropium+salmeterol combination was statistically significant (P=0.01). The FEV1 AUCs0−24h were 2.854l (95% CI: 1.928–3.780) for tiotropium, 2.786l (95% CI: 1.913–3.660) for salmeterol, and 3.640l (95% CI: 2.674–4.605) for tiotropium+salmeterol. All differences between treatments were not statistically significant (P>0.05). These results seem to indicate that the use of the tiotropium+salmeterol combination is more efficacious than the single agents alone, but the once-daily administration of the two drugs is inadvisable due to the broncholytic profile of salmeterol