Tiotropium for stable chronic obstructive pulmonary disease: a meta-analysis

R Graham Barr ^1*, Jean Bourbeau ², Carlos A Camargo, Jr. ³ and Felix S F Ram ⁴

¹ Columbia University, United States
² McGill University Health Centre, Canada
³ Massachusetts General Hospital, United States
⁴ Massey University, New Zealand

^* To whom correspondence should be addressed. E-mail: rgb9{at}columbia.edu.

Accepted 16 June 2006

Abstract

Objective: To evaluate the efficacy of tiotropium, a long-acting anticholinergic therapy, on clinical events, symptom scales, pulmonary function and adverse events in stable chronic obstructive pulmonary disease (COPD).

Data sources: A compilation of systematic searches of the Cochrane Trials database, MEDLINE, EMBASE, CINAHL and hand-search of 20 respiratory journals. Missing data were obtained from authors and the manufacturer.

Design: A systematic review of high quality randomised controlled trials.

Review methods: Randomised trials of 12 week's duration comparing tiotropium to placebo, ipratropium bromide, or long-acting 2-agonists (LABA). Studies were pooled to yield odds ratios (OR) or weighted mean differences with 95% confidence intervals (CI).

Results: Nine trials (8,002 patients) met inclusion criteria. Tiotropium reduced the odds of a COPD exacerbation (OR 0.73; 95% CI, 0.66 to 0.81) and related hospitalisation (OR 0.68; 95% CI, 0.54 to 0.84) but not pulmonary (OR 0.50; 95% CI, 0.19 to 1.29) or all-cause (OR 0.96; 95% CI, 0.63 to 1.47) mortality compared to placebo and ipratropium. Reductions in exacerbations and hospitalisations compared to LABA were not statistically significant. Similar patterns were evident for quality-of-life and symptom scales. Tiotropium yielded greater increases in FEV1 and FVC from baseline to 6-12 months than did placebo, ipratropium and LABA. Decline in FEV1 over one year was 30 ml (95% CI, 7 to 53 ml) slower with tiotropium than with placebo and ipratropium (data were not available for LABA). Reports of dry mouth and urinary tract infections were increased with tiotropium.

Conclusions: Tiotropium reduced COPD exacerbations and related hospitalisations. In addition, tiotropium improved quality-of-life and symptoms, and may have slowed decline in FEV1. Long-term trials are warranted to evaluate the effects of tiotropium on decline in FEV1 and to clarify its role compared to LABA.

Keywords: bronchodilator agents, cholinergic antagonists, chronic bronchitis, chronic obstructive pulmonary disease, emphysema

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