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

The 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-mug tiotropium, 50-mug salmeterol, and 18-mug tiotropium + 50-mug salmeterol were given. Serial measurements of forced expiratory volume in 1 s (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 4 h after inhalation of tiotropium or salmeterol and 3 h 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: 0.0180-0.120; 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 24 h, 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 + satmeterol 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 (AUCs(0-12h)) 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 + satmeterol combination was statistically significant (P = 0.01). The FEV1 AUCs(0-24h) 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 + satmeterol 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. (C) 2004 Published by Elsevier Ltd.