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.

Background

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

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 baseline, a small but statistically significant increase in adjusted mean heart rate was observed for tiotropium 5 µg (+1.6 beats per minute [bpm]; P=0.0010), but no difference was observed for olodaterol 5 µg (+0.3 bpm; P=0.2778) or tiotropium/olodaterol 5/5 µg (-0.1 bpm; P=0.4607). MACE and fatal MACE were limited to 1 to 3 patients across treatment groups.

Conclusion

Compared with the compounds given as monotherapy, treatment with tiotropium/olodaterol fixed-dose combination therapy is not associated with medically relevant or statistically significant effects on arrhythmia as assessed by Holter ECG. Based on these findings, there is no evidence to assume a clinically relevant impact on cardiac function from dual tiotropium/olodaterol treatment.

Trial Registration

TONADO 1 (ClinicalTrials.gov: NCT01431274); TONADO 2 (ClinicalTrials.gov: NCT01431287).

Informations de copyright

© 2020 Andreas et al.

Déclaration de conflit d'intérêts

SA reports personal fees from Boehringer Ingelheim and GlaxoSmithKline, and payments for presenting from Boehringer Ingelheim, AstraZeneca, Berlin Chemie, Chiesi and Novartis, outside the submitted work. UB, AdlH, IK and MT are employees of Boehringer Ingelheim. PA reports grants from the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET), AstraZeneca, GlaxoSmithKline, Grifols Deutschland, MSD Sharp & Dohme, Pfizer, Takeda, Boehringer Ingelheim and Novartis Deutschland, grants and non-financial support from Bayer Schering Pharma AG and Chiesi, and grants, personal fees and non-financial support from Novartis Deutschland, outside the submitted work. The authors report no other conflicts of interest in this work.