Tiotropium (Spiriva) is a bronchodilator drug that has been developed to open the airways in the lungs effectively with once daily dosing. The main aims of therapy in COPD are to reduce exacerbations and related hospitalisations, improve quality of life, and reduce the rate of decline in lung function. The evidence from the trials in the review indicates that, compared with a placebo and ipratropium, tiotropium does reduce exacerbations and related hospitalisations and improves quality of life and symptoms in people with moderately severe COPD, although the evidence with regards to decline in lung function is less clear. Tiotropium caused dry mouth. Compared with other commonly used drugs in COPD, such as long-acting beta agonists (including salmeterol), there is not enough evidence for us to draw reliable conclusions. In order to better understand the effects of this drug we need long-term studies (over several years), studies conducted in mild and severe COPD, and additional studies that measure outcomes in relation to other agents used in the treatment of this condition.
Tiotropium reduced COPD exacerbations and related hospitalisations compared to placebo and ipratropium. It also improved health-related quality-of-life and symptom scores among patients with moderate and severe disease, and may have slowed decline in FEV1. Additional long-term studies are required to evaluate its effect on mortality and change in FEV1 to clarify its role in comparison to, or in combination with, long-acting ß2-agonists and to assess its effectiveness in mild and very severe COPD.
Tiotropium is a new anticholinergic therapy for chronic obstructive pulmonary disease (COPD) that differs from ipratropium by its functional relative selectivity for muscarinic receptor subtypes and which allows once-per-day dosing.
To determine the efficacy of tiotropium on clinical endpoints such exacerbations and hospitalisations, symptom scales and pulmonary function compared to placebo and other bronchodilators used for stable COPD.
Randomised controlled trials (RCTs) were identified from the Cochrane Airways Review Group Specialised Register, a compilation of systematic searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL, and hand searching of 20 respiratory journals. Bibliographies from included studies and reviews were searched. The date of the last search was October 2004.
Randomised clinical trials comparing tiotropium with placebo, ipratropium bromide, or long-acting ß2-agonists for greater than, or equal to, one month's duration.
Two reviewers independently extracted data. Missing data were obtained from authors or the manufacturer of tiotropium. The data were analysed using the Cochrane Review Manager RevMan 4.2. Studies were pooled to yield weighted mean differences (WMD) or odds ratios (OR) and reported using 95% confidence intervals (CI).
From 69 identified references, nine RCTs (6,584 patients) met inclusion criteria. Tiotropium reduced the odds of a COPD exacerbation (OR 0.74; 95% CI 0.66 to 0.83) and related hospitalisations (OR 0.64; 95% CI 0.51 to 0.82) compared to placebo or ipratropium. When applied to an annual baseline risk of 45% for exacerbations and 10% for hospitalisation, the number of patients needed to treat with tiotropium for one year were 14 (95% CI 11 to 22) to prevent one exacerbation and 30 (95% CI 22 to 61) to prevent one hospitalisation compared to placebo and ipratropium. Reductions in these endpoints compared to long-acting ß2-agonists were not statistically significant. Similar patterns were evident for quality-of-life and symptom scales. Increases in FEV1 and FVC from baseline were significantly larger with tiotropium than with placebo, ipratropium and long-acting ß2-agonists over 6 to 12 months. The decline in trough FEV1 from steady state was 30 ml (95% CI 7 to 53 ml) less with tiotropium than with placebo or ipratropium over one year; no data on decline in FEV1 from steady state were available for long-acting ß2-agonists. Dry mouth was increased by tiotropium.