Eleven RCTs were included in the review (n=1,006, range 40 to 221). Five RCTs scored 5 points out of five for validity, two scored 4 points, four scored 3 points and one scored 2 points. Ten studies were double-blinded.
Pulmonary function: When tiotropium was compared with either placebo or ipratropium, there was a significantly greater improvement in the tiotropium group for both FEV1 (WMD 304mL, 95% CI 271 to 337; six RCTs) and FEV1% (WMD 8.35%, 95% CI 5.40 to 11.31; four RCTs).
Other outcomes: When tiotropium was compared with either placebo or ipratropium, the rate of symptom improvement was significantly higher in the tiotropium group (RR 2.0, 95% CI 1.61 to 2.49, NNT=6, 95% CI 5 to 9; four RCTs). When tiotropium was compared with placebo, the rate of COPD exacerbation was significantly reduced in the tiotropium group (RR 0.07, 95% CI: 0.01 to 0.54; two RCTs). There was no statistically significant difference in the rate of COPD exacerbation between tiotropium and ipratropium (one RCT). There was no significant difference in the risk of adverse events in the tiotropium group compared with placebo. Adverse event rates were comparable when tiotropium was compared with ipratropium (six RCTs).
No significant statistical heterogeneity was found for any of the above analyses (I2=0%). There was no clear evidence of publication bias. Sensitivity and subgroup analyses did not materially affect any of the results.