Background: Tiotropium is a long-acting inhaled anticholinergic developed for the treatment of chronic obstructive pulmonary disease (COPD) and has been available since 2002. We sought to update an evaluation of the safety of tiotropium in the HandiHaler formulation as significant clinical trial data have become available over time.
Methods: Pooled analysis of adverse event reporting from phase III and IV tiotropium HandiHaler clinical trials with the following characteristics was performed: randomized, double-blind, parallel group, placebo-controlled design, tiotropium 18 microg once-daily dosing, COPD indication, duration of at least four weeks. Incidence rates by treatment group, rate differences (tiotropium-placebo), and 95% confidence intervals were determined.
Results: Twenty-six trials were identified involving 17,014 patients. Mean age was 65 years, mean forced expiratory volume in one second was 1.16 L (41% predicted), 76% men. Total exposure to study drug was 11,958 patient-years (tiotropium) and 10,578 patient-years (placebo). Tiotropium was associated with a reduced risk (expressed as rate difference [95% confidence interval] per 100 patients-years at risk) for an adverse event (-17.5 [-22.9, -12.2]), serious adverse event (-1.41 [-2.81, -0.00]) and a fatal event (-0.63 [-1.14, -0.12]). A reduced risk was present for adverse events that were cardiac (-0.79 [-1.48, -0.09]), lower respiratory (-14.2 [-17.0, -11.5]) and for a composite endpoint of major adverse cardiovascular events (-0.45 [-0.85, -0.05]). Typical expected inhaled anticholinergic effects such as dry mouth, constipation, and urinary difficulties were observed in the safety database.
Conclusion: The safety data review does not indicate an increased risk for death or cardiovascular morbidity during tiotropium treatment in patients with COPD.
Keywords: chronic obstructive pulmonary disease; mortality; safety; tiotropium.