Thirteen RCTs were included (n=6,078). The trial quality Jadad score ranged from 2 to 5. The majority of trials had a quality score of 3. Sample sizes ranged from 31 to 1,829 patients.
Tiotropium versus placebo:
Tiotropium significantly reduced chronic obstructive pulmonary disease exacerbations compared to placebo (odds ratio 0.76, 95% CI: 0.66, 0.87, p=0.0001, number needed to treat 21, 95% CI: 13, 50, eight trials). Hospital admissions were significantly reduced with tiotropium compared to placebo (odds ratio 0.59, 95% CI: 0.47, 0.73, p=0.0001, number needed to treat 20, 95% CI: 14, 34, three trials). The difference in all-cause mortality between tiotropium and placebo groups (four trials) was not statistically significant and there was no significant statistical heterogeneity detected for these outcomes.
Tiotropium versus ipratropium:
Primary outcome data were not available. Tiotropium significantly improved mean change in trough FEV1 (forced expiratory outflow in the first second) and FVC (forced vital capacity) from baseline compared with ipratropium (two trials); tiotropium with a weighted mean difference of 0.15L (95% CI: 0.11, 0.18, p=0.0001); and ipratropium with a weighted mean difference of 0.22L (95% CI: 0.31, 0.31, p=0.0001). The mean change in peak FEV1 and FVC were also increased in the tiotropium group compared to ipratropium: tiotropium with a weighted mean difference of 0.10 (95% CI: 0.06, 0.14, p=0.0001); and ipratropium with a weighted mean difference of 0.09 (95% CI: 0.01, 0.08, p=0.05). No significant heterogeneity was detected.
Tiotropium versus long-acting beta-agonists:
Hospital admissions were significantly reduced in the tiotropium group compared with salmeterol (odds ratio 0.67, 95% CI: 0.46, 0.98, p=0.04, number needed to treat 33, 95% CI: 17, 1007, n=1,460 patients). No heterogeneity was detected. There was no significant difference in chronic obstructive pulmonary disease exacerbations with tiotropium compared with long-acting beta-agonists. There was evidence of heterogeneity between studies (I2=55.6%). Sensitivity analyses showed that statistical heterogeneity was due to methodological quality.
Further analyses were reported.