No Influence on Cardiac Arrhythmia or Heart Rate from Long-Term Treatment with Tiotropium/Olodaterol versus Monocomponents by Holter ECG Analysis in Patients with Moderate-to-Very-Severe COPD

Stefan Andreas,1,2 Ulrich Bothner,3 Alberto de la Hoz,3 Isabel Kloer,3 Matthias Trampisch,3 Peter Alter4 1Department of Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany; 2LungClinic Immenhausen, Immenhausen, Germany, Member of the German Center for Lung Research (DZL); 3Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany; 4Department of Medicine, Pulmonary and Critical Care Medicine, Philipps University of Marburg (UMR), Marburg, Germany, Member of the German Center for Lung Research (DZL)Correspondence: Stefan AndreasDepartment of Cardiology and Pneumology, Robert-Koch-Str. 40., Göttingen, GermanyTel +49 05673 501 1112Fax +49 05673 501 1101Email stefan.andreas@med.uni-goettingen.deBackground: Patients with chronic obstructive pulmonary disease (COPD) and cardiovascular comorbidities may have an increased risk of medication-related cardiac arrhythmias. We therefore performed an analysis of Holter electrocardiogram (ECG) data from two large, long-term, controlled clinical COPD trials to investigate whether tiotropium/olodaterol increased the risk of cardiac arrhythmia and mean heart rate.Methods: We analyzed Holter ECG data from a representative subset of patients (N=506) from the two pooled replicate studies (TONADO 1 and 2) assessing tiotropium/olodaterol 5/5 μg therapy versus tiotropium 5 μg or olodaterol 5 μg monotherapy, inhaled once daily (two single inhalations) using the Respimat® Soft Mist™ inhaler device. Additionally, major adverse cardiac events (MACE) with tiotropium/olodaterol were assessed versus the respective monotherapies.Results: After 12 weeks of treatment, there was no difference in the number of patients who had an increase or decrease from baseline in 24-hour supraventricular premature beats or ventricular premature beats between tiotropium/olodaterol 5/5 μg combination therapy and its monocomponents. Compared with baselin