Sixteen RCTs (n=16,301 patients) were included in the review. Trials had Jadad scores that ranged from 3 to 5 points, which indicated adequate quality. Follow-up ranged from 12 to 208 weeks.
Health-related quality of life (seven RCTs): Tiotripium was associated with a significantly greater and clinically important change in quality of life when compared with placebo (OR 1.61, 95% CI 1.38 to 1.88; Ι²=41.6%; six RCTs) or ipratropium (OR 2.03, 95% CI 1.34 to 3.07; one RCT) in patients with chronic obstructive pulmonary disease (COPD). There was no evidence of a significant difference in quality of life in one study when tiotropium was compared to salmeterol.
Dyspnoea: Tiotropium was associated with a significantly greater and clinically important reduction in dyspnoea when compared with placebo (OR 1.96, 95% CI 1.58 to 2.44; Ι²=0%; two RCTs) or ipratropium (OR 2.10, 95% CI 1.28 to 3.44; number of RCTs not reported). There was no evidence of a significant difference in the incidence of dyspnoea when tiotropium was compared with salmeterol.
COPD exacerbations (13 RCTs): Tiotropium was associated with a significant reduction in the rate of COPD exacerbations when compared with placebo (OR 0.83, 95% CI 0.72 to 0.94; Ι²=49.7%; 11 RCTs) or ipratropium (OR 0.64, 95% CI 0.44 to 0.92; one RCT). There was no evidence of a significant difference in the rate of COPD exacerbations in two RCTs when tiotropium was compared with salmeterol.
COPD exacerbation-related hospitalisation (nine studies): Tiotropium was associated with significantly fewer hospitalisations when compared with placebo (OR 0.89, 95% CI 0.80 to 0.98; Ι²=18.2%; seven RCTs). A similar but non significant reduction was found when tiotropium was compared with salmeterol (OR 0.54. 95% CI 0.29 to 1.00; Ι²=0%; two RCTs). There was no evidence of a significant association when tiotropium was compared with ipratropium (one RCT) or formoterol (one RCT).
Adverse events: Tiotropium was associated with a greater incidence of dry mouth when compared with placebo (OR 3.19, 95% CI 1.79 to 5.70; Ι²=59%; eight RCTs), salmeterol (OR 4.60, 95% CI 2.37 to 8.93; Ι²=0%; two RCTs) or ipratropium (OR 3.09, 95% CI 1.68 to 5.66; Ι²=0%; two RCTs). Compared with salmeterol, tiotropium was associated with a statistically significant lower risk of a serious adverse event (OR 0.39, 95% CI 0.16 to 0.95; one RCT), but there was no evidence of significant differences in the incidence of serious adverse events in seven RCTs where tiotropium was compared with placebo.
Sensitivity analysis, with the removal of longer term trials (over one year) indicated that significant differences between tiotropium and placebo in health-related quality of life, COPD exacerbations and hospitalisations. The rate of serious adverse events remained non significant.