OBJECTIVES: We searched the Cochrane Airways Group's Specialised Register of Trials (CAGR) and ClinicalTrials.gov up to February 2012.
SELECTION CRITERIA: Two review authors independently assessed studies for inclusion and then extracted data on study quality and the outcome results. We contacted study authors and trial sponsors for additional information, and collected information on adverse effects from all trials. We analysed the data using Cochrane Review Manager 5, RevMan 5.1.
MAIN RESULTS: This review included 22 studies of good methodological quality that had enrolled 23,309 participants with
COPD. The studies used similar designs, however, the duration varied from three months to four years. In 19 of the studies, 18 μg
tiotropium once daily via the Handihaler
dry powder inhaler was evaluated, and in three studies, 5 or 10 μg
tiotropium once daily via the Respimat soft mist
inhaler was evaluated. Compared to placebo,
tiotropium treatment significantly improved the mean quality of life (mean difference (MD) -2.89; 95% confidence interval (CI) -3.35 to -2.44), increased the number of participants with a clinically significant improvement (odds ratio (OR) 1.52; 95% CI 1.38 to 1.68), and reduced the number of participants with a clinically significant deterioration (OR 0.65; 95% CI 0.59 to 0.72) in quality of life (measured by the St George's Respiratory Questionnaire (SGRQ)).
Tiotropium treatment significantly reduced the number of participants suffering from exacerbations (OR 0.78; 95% CI 0.70 to 0.87). This corresponds to a need to treat 16 patients (95% CI 10 to 36) with
tiotropium for a year in order to avoid one additional patient suffering exacerbations, based on the average placebo event rate of 44% from one-year studies.
Tiotropium treatment led to fewer hospitalisations due to exacerbations (OR 0.85; 95% CI 0.72 to 1.00), but there was no statistically significant difference in all-cause hospitalisations (OR 1.00; 95% CI 0.88 to 1.13) or non-fatal serious adverse events (OR 1.03; 95% CI 0.97 to 1.10). Additionally, there was no statistically significant difference in all-cause mortality between the
tiotropium and placebo groups (Peto OR 0.98; 95% CI 0.86 to 1.11). However, subgroup analysis found a significant difference between the studies using a
dry powder inhaler and those with a soft mist
inhaler (test for subgroup differences: P = 0.01). With the
dry powder inhaler there were fewer deaths in the
tiotropium group (Peto OR 0.92; 95% CI 0.80 to 1.05) than in the placebo group (yearly rate 2.8%), but with the soft mist
inhaler there were significantly more deaths in the
tiotropium group (Peto OR 1.47; 95% CI 1.04 to 2.08) than in the placebo group (yearly rate 1.8%). It is noted that the rates of patients discontinuing study treatment were uneven, with significantly fewer participants withdrawing from
tiotropium treatment than from placebo treatment (OR 0.66; 95% CI 0.59 to 0.73). Participants on
tiotropium had improved lung function at the end of the study compared with those on placebo (trough forced expiratory volume in one second (FEV(1)) MD 118.92 mL; 95% CI 113.07 to 124.77).
AUTHORS' CONCLUSIONS: This review shows that
tiotropium treatment was associated with a significant improvement in patients' quality of life and it reduced the risk of exacerbations, with a number needed to treat to benefit (NNTB) of 16 to prevent one exacerbation.
Tiotropium also reduced exacerbations leading to hospitalisation but no significant difference was found for hospitalisation of any cause or mortality. Thus,
tiotropium appears to be a reasonable choice for the management of patients with stable
COPD, as proposed in guidelines. The review however, shows that
tiotropium delivered via the Respimat soft mist
inhaler was associated with a significantly increased risk of mortality compared with placebo, which calls for caution with this device whilst awaiting the results of an ongoing head-to-head trial comparing
tiotropium delivery devices and doses.