Hodder et al FVC TDI focal score SGRQ total score Trough Peak AUC 0–3 *p < 0.05, **p < 0.001 vs placebo; † p < 0.05, tiotropium vs salmeterol. (b) Treatment response (exacerbations) after 169 days % patients with >1 exacerbation Exacerbations/patient-year (% reduction vs placebo) Exacerbation days/patient-year *p = 0.047, **p = 0.135 vs placebo. 220 + 40** † 400 + 40** † 370 + 40** † 1.03 + 0.4* –3.27 + 1.2* Tiotropium 40% 1.36 (–23%)* 21.9 Table 3 Outcomes in patients using ICS (tiotropium: n = 259; salmeterol: n = 278; placebo: n = 259) (a) Treatment response (spirometry,TDI, and SGRQ score) after 169 days Tiotropium vs placebo Salmeterol vs placebo Trough 110 + 20** 80 + 20** FEV1 Peak 220 + 30** † 150 + 30** AUC 0–3 190 + 20** † 130 + 20** 130 + 40** 220 + 40** 230 + 40** 0.57 + 0.4 –1.12 + 1.2 Salmeterol 40% 1.46 (–17%)** 26.9 Placebo 45% 1.76 29.3 In the original study population there was a relatively low number of exacerbations, and in the current subgroup analysis only 27% of placebo patients without ICS and 45% of placebo patients concurrently treated with ICS experienced any exacerbation during the 6-month observation period. Although in the original study patients using ICS had expe- rienced more exacerbations (1.76 exacerbations per patient per year in the placebo group) than patients without ICS (1.0 exacerbations/patient/year, placebo), because patients were not randomized to ICS or non-ICS groups, it should be stressed that a comparison of these sub-groups is of lim- ited value. This apparent difference in exacerbation rates according to concurrent ICS use may simply indicate that the patients’ physicians had prescribed ICS for those patients they felt to have the most unstable COPD. The trend towards a reduced number of exacerbations experienced by the patients of this subgroup analysis receiving tiotropium (–23%) and salmeterol (–17%) did not reach statistical signiﬁcance, but the magnitude of effect resembled that observed in the original study population (Brusasco et al 2003). A recently reported prospective trial comparing the addition of combined salme- terol/ﬂuticasone, salmeterol alone, or placebo with COPD patients receiving tiotropium was also unable to demonstrate a statistically signiﬁcant difference in COPD exacerbation frequency amongst the treatment groups, but compared with placebo, the group treated with tiotropium plus salmeterol/ 0 –1 e r o lsc –2 a t o tQ–3 R G S–4 –5 ** Change to baseline ns Tiotropium Salmeterol Placebo ** p < 0.01 vs. placebo ns = not significant vs. placebo Figure 3 Improvement in health-related quality of life in active treatment groups compared to baseline SGRQ Total score (patients concurrently using ICS). 164 International Journal of COPD 2007:2(2)