Twenty-four publications were included for review. There were 16 double-blind RCTs (n=13,584 patients) plus four secondary analyses (from two of the included RCTs) and four subgroup analyses (from two of the included RCTs).
Tiotropium versus placebo (nine RCTs; four secondary analyses and four subgroup analyses; n=10,291)
Eight trials of primary data compared tiotropium with placebo on the St Georges Respiratory Questionnaire (SGRQ). Six trials reported statistically significant benefits with tiotropium (p-values ranged from <0.05 to <0.001). The differences between tiotropium and placebo were clinically meaningful in only two of these trials. However, significantly more patients who received tiotropium achieved clinically significant change compared with patients who received placebo in five trials (p<0.05 to p<0.001). Subgroup analyses revealed that statistically and clinically significant benefits were observed with tiotropium compared with placebo in GOLD stage II patients, patients who did not receive maintenance therapy at baseline and patients who smoked. Five trials of primary data compared tiotropium with placebo on the Transition Dyspnoea Index (TDI). Three reported statistically and clinically significant benefits with tiotropium (p=0.03 to p<0.001). Tiotropium significantly improved physical but not mental health domains on the Short Form 36 (SF-36; one trial; p<0.05).
Tiotropium versus active comparators (eight RCTs; n=4,500)
Tiotropium showed significant benefits as measured on SGRQ compared with ipratropium (one trial; n=535; p=0.004) and salmeterol (one trial; n=1,207; p<0.01). However, tiotropium showed significantly less improvement on the SGRQ compared with salmeterol plus fluticasone (one trial; n=1,323; p=0.038). Tiotropium was superior to ipratropium (p<0.05) but not salmeterol in improving TDI scores. Tiotropium dual therapy with salmeterol significantly improved SGRQ scores (one trial; p=0.02), but not TDI scores compared with tiotropium alone. Two trials (n=285) evaluated tiotropium combined with formoterol; in one trial TDI scores significantly improved (p=0.0002), but SGRQ scores did not compared with tiotropium monotherapy. Tiotropium triple therapy (three trial; n=1,150) significantly improved SGRQ scores in two trials compared with tiotropium monotherapy (p=0.02 and 0.023) and significantly improved TDI scores in one trial (p<0.001).