Electrophysiological effects of a single intravenous administration of ivabradine (S 16257) in adult patients with normal baseline electrophysiology.
BACKGROUND
Ivabradine is a heart rate-lowering agent that selectively inhibits the pacemaker current, I(f), in the sinoatrial node. The objective of this study was to evaluate the effects of a single intravenous administration of ivabradine on cardiac electrophysiological parameters in patients with normal baseline electrophysiology. The safety profile of ivabradine was also investigated.


METHODS
This was an open-label, single-dose, non-controlled study conducted at one centre. Patients received a single dose of ivabradine (0.2 mg/kg) intravenously as a slow bolus over 15 seconds. Electrophysiological investigations, after catheter ablation for cardiac dysrhythmia, were performed at baseline and 30 minutes and 1 hour after drug administration. Electrode catheters were introduced and advanced to the right atrium, the bundle of His and the right ventricular apex of the heart. Electrophysiological parameters assessed included heart rate, QT interval, corrected QT interval (QTc), PR interval, sinoatrial conduction time, sinus node recovery time, and right atrial and ventricle refractory periods. Changes in electrophysiological parameters over time were assessed using one-way analysis of variance. In the case of a significant time effect, the Newman-Keuls procedure was used for comparison.


METHODS
A total of 14 patients, 12 male and 2 female, aged 18-75 years were included in the study. The arrhythmia requiring catheter ablation was atrioventricular (AV) excitation in seven patients, paroxysmal supraventricular tachycardia in five patients, atrial fibrillation and flutter in one patient, and cardiac dysrhythmia in one patient. All patients had normal electrophysiology at baseline.


RESULTS
Mean heart rate decreased significantly with ivabradine by 12.9 beats/min at 30 minutes and 14.1 beats/min at 1 hour. The mean QT interval increased but QTc showed no significant change from baseline. The PR and QRS intervals were unchanged. The right atrial and right ventricle refractory periods showed no significant change from baseline. The measured QT interval and the sinus node recovery time were increased. There were no clinically relevant changes in any other major electrophysiological parameters. Ivabradine was well tolerated and no serious adverse events occurred.


CONCLUSIONS
A single intravenous dose of ivabradine had a significant heart rate-lowering effect, observed at 30 minutes and 1 hour after administration. Ivabradine did not prolong QTc or modify conductivity and refractoriness of the atrium, AV node, His-Purkinje system and ventricles, or repolarisation duration. These results confirm the action of ivabradine as a specific heart rate-lowering agent.
Camm
A John
AJ
The Medical School, St George's Hospital, London, UK. jcamm@sghms.ac.uk
Lau
Chu-Pak
CP
D000293:Adolescent; D000328:Adult; D001552:Benzazepines / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects*; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007275:Injections, Intravenous; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D001552:Benzazepines; D000077550:Ivabradine