OBJECTIVE: To systematically review recent evidence on the effectiveness of tiotropium versus placebo, ipratropium, and long-acting β(2) agonists on outcomes relevant to patients with stable COPD, including health-related quality of life, dyspnea, exacerbations and hospitalizations. METHODS: Our inclusion criteria for trials were: ≥ 12 weeks; compared tiotropium to placebo, ipratropium, or long-acting β agonists; patients ≥ 40 y old and with stable COPD. Sixteen trials (16,301 patients) met the inclusion criteria. RESULTS: Tiotropium improved health-related quality of life (measured with St George's Respiratory Questionnaire) compared to placebo (odds ratio [OR] 1.61, 95% CI 1.38-1.88, P < .001) and ipratropium (OR 2.03, 95% CI 1.34-3.07, P = .001). Tiotropium also improved dyspnea (measured with the Transitional Dyspnea Index) compared to placebo (OR 1.96, 95% CI 1.58-2.44, P < .001) and ipratropium (OR 2.10, 95% CI 1.28-3.44, P = .003). Tiotropium decreased the likelihood of an exacerbation (OR 0.83, 95% CI 0.72-0.94, P = .004) and related hospitalizations (OR 0.89, 95% CI 0.80-0.98, P = .02) but not serious adverse events (OR 1.06, 95% CI 0.97-1.17, P = .19), compared to placebo. The cumulative incidence of dry mouth was 7.4% with tiotropium, compared to 3.9% with ipratropium, 1.6% with salmeterol, and 2.0% with placebo. CONCLUSIONS: In stable COPD, tiotropium showed superior efficacy in improving quality of life and dyspnea, compared to placebo and ipratropium. However, tiotropium's differences with salmeterol were less clear.
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