CHRONIC OBSTRUCTIVE PULMONARY DISEASE Tiotropium for stable chronic obstructive pulmonary disease: a meta-analysis

Background: A systematic review was undertaken to evaluate the efficacy of tiotropium, a long acting anticholinergic drug, on clinical events, symptom scales, pulmonary function, and adverse events in stable chronic obstructive pulmonary disease (COPD). Methods: A systematic search was made of the Cochrane trials database, MEDLINE, EMBASE, CINAHL, and a hand search of 20 respiratory journals. Missing data were obtained from authors and the manufacturer. Randomised controlled trials of >12 weeks’ duration comparing tiotropium with placebo, ipratropium bromide, or long acting b2 agonists (LABA) were reviewed. Studies were pooled to yield odds ratios (OR) or weighted mean differences with 95% confidence intervals (CI). Results: Nine trials (8002 patients) met the 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 with placebo and ipratropium. Reductions in exacerbations and hospitalisations compared with LABA were not statistically significant. Similar patterns were evident for quality of life and symptom scales. Tiotropium yielded greater increases in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) from baseline to 6–12 months than did placebo, ipratropium, and LABA. Decline in FEV1 over 1 year was 30 ml (95% CI 7 to 53) 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, improved quality of life and symptoms, and may have slowed the decline in FEV1. Long term trials are warranted to evaluate the effects of tiotropium on decline in FEV1 and to clarify its role compared with LABA.