Holter ECG-based arrhythmia and heart rate analysis in patients with COPD receiving a fixed-dose combination of tiotropium/olodaterol versus its monocomponents

Introduction Patients with COPD frequently exhibit cardiovascular comorbidities and are at risk of cardiac arrhythmias. To evaluate potential class effects of long-acting muscarinic antagonists (LAMAʼs) and long-acting β2-agonists (LABAʼs) on an increased arrhythmia risk in COPD patients, further investigation is required.

Aims To analyse Holter ECG data from the TONADO 1 +2 studies to assess the effect of tiotropium

(5 µg)/olodaterol (5 µg) (T/O) combination therapy vs. monocomponents (Tio or Olo) on cardiac arrhythmia endpoints.

Methods Holter ECG monitoring was performed on a subset of patients (N = 506) in two Phase III, replicate, multicentre studies at baseline and 12 weeks. Records were evaluated for 24-hour mean heart rate (HR), supraventricular premature beats (SVPBs) and ventricular premature beats (VPBs).

Results No pro-arrhythmic SVPB or VPB effect was observed for T/O vs. Tio and Olo. The proportions of patients showing a decrease, increase or no change in SVPB and VPB from baseline was comparable across treatment groups (Figure). The change in mean HR from baseline to Week 12 was small and not clinically relevant in all treatment groups (−0.6 for T/O, 1.8 for Tio and 0.5 for Olo).

Conclusions Treatment with T/O combination therapy and its monocomponents is not associated with an increased rate of arrhythmias or heart rate as assessed by Holter ECG.