Background: Patients with chronic obstructive pulmonary disease (COPD) are at risk of developing cardiac arrhythmias and elevated heart rate. A theoretical mechanistic association based on the interaction of long-acting beta2-agonists (LABAs) with adrenoreceptors in the heart and vasculature is assumed as a potential class-related risk. Therefore, we performed a pooled analysis of Holter electrocardiogram (ECG) data from four 48-week, randomized, double-blind, placebo-controlled, parallel-group, Phase III clinical trials evaluating olodaterol (5 mug or 10 mug) or formoterol (12 microg) versus placebo. Methods: We analyzed Holter ECG data from a representative subset of 775 patients with Global Initiative for Chronic Obstructive Lung Disease stage 2-4 COPD from four studies (1222.11-14) assessing olodaterol (5 mug and 10 mug) and formoterol (12 microg) versus placebo. Results: No statistically significant (P>0.3) or clinically relevant differences in the shift from baseline of premature supraventricular or ventricular beats were observed among the active treatment and the placebo groups. Minor and transient differences were observed in the adjusted mean heart rate from baseline during treatment in all groups. There was a numerically small but statistically significant increase for formoterol at Week 24, olodaterol 5 mug at Weeks 12 and 40, and olodaterol 10 mug at Week 40 (all less than 3.0 beats per minute). Mean heart rates returned to a statistically non-significant change at Week 48 for all treatment groups. No increase in major adverse cardiovascular events was observed. Conclusion: Treatment with olodaterol or formoterol is not associated with arrhythmias or a persistent increase in heart rate as assessed by Holter ECG in patients with COPD. Trial Registration: ClinicalTrials.gov identifiers: NCT00782210 (1222.11); NCT00782509 (1222.12); NCT00793624 (1222.13); NCT00796653 (1222.14).
- Andreas, S.
- Bothner, U.
- de la Hoz, A.
- Kloer, I.
- Trampisch, M.
- Alter, P.
Keywords
- *Holter ECG
- *arrhythmia
- *formoterol
- *heart rate
- *olodaterol
- 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, grants, personal
- fees and non-financial support from Novartis Deutschland, and grants and personal
- fees from Novartis Deutschland, outside the submitted work. The authors report no
- other conflicts of interest in this work.