Evaluating cardiac safety of tiotropium in patients with COPD: Combined analysis of Holter-ECG data from four trials

Background: Extensive clinical trial data have shown that different doses of tiotropium, administered via either HandiHaler® 18 µg (HH18) or Respimat®, improves lung function, quality of life and reduces exacerbations in patients with chronic obstructive pulmonary disease (COPD); however, there is concern that antimuscarinic agents may induce cardiac arrhythmias in a vulnerable subpopulation of patients with cardiovascular comorbidity. Aims and objectives: To support the cardiac safety of tiotropium maintenance therapy by investigating heart rate and arrhythmia parameters. Methods: Combined analysis of all tiotropium trials (HH18 and/or R1.25 – 10) in COPD involving Holter-electrocardiogram (ECG) monitoring conducted between 2003 and 2012. Men and women aged= 40 years with a smoking history of= 10 pack-years, and a clinical diagnosis of COPD were included. Holter-ECGs were evaluated for heart rate (HR), supraventricular premature beats (SVPBs), ventricular premature beats (VPBs) and pauses. Quantitative and categorical endpoints were derived for each of the Holter-monitoring days. Results: Four trials (n= 727 patients) were included, ranging from 4 – 48 weeks' treatment duration. Mean age was 64.7 years. Neither R1.25 – 10 nor HH18 were associated with changes in HR, SVPBs, VPBs and pauses compared to placebo or the pretreatment baseline period. There was no evidence of an exposure-effect relationship for the cardiac arrhythmia endpoints. Conclusion: Tiotropium maintenance therapy with R1.25 – 10 or HH18 was well tolerated and not associated with an increased risk of cardiac arrhythmia in patients with COPD in this analysis. Funded by Boehringer Ingelheim and Pfizer. Presented at ERS congress 2014