Inhaled tiotropium for stable chronic obstructive pulmonary disease.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.


METHODS
Randomised clinical trials comparing tiotropium with placebo, ipratropium bromide, or long-acting ss2-agonists for greater than, or equal to, one month's duration.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Barr
R G
RG
Division of General Medicine, PH-9 East Room 105, Columbia-Presbyterian Medical Center, 622 West 168th Street, New York, NY 10032, USA. rgb9@columbia.edu
Bourbeau
J
J
Camargo
C A
CA
Ram
F S F
FS
D000280:Administration, Inhalation; D018680:Cholinergic Antagonists / Q000008:administration & dosage*; D006801:Humans; D009241:Ipratropium / Q000008:administration & dosage; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012602:Scopolamine Derivatives / Q000008:administration & dosage*; D013147:Spirometry; D000069447:Tiotropium Bromide
D018680:Cholinergic Antagonists; D012602:Scopolamine Derivatives; D009241:Ipratropium; D000069447:Tiotropium Bromide