Vernakalant

Zusammenfassung

Vernakalant ist ein vielversprechendes neuartiges Antiarrhythmikum zur intravenösen Konversion von Vorhofflimmern in Sinusrhythmus. Es hemmt mehrere Ionenströme inklusive I_Kr und unterscheidet sich von herkömmlichen Antiarrhythmika durch eine relative Vorhofselektivität. Erreicht wird dies durch eine Hemmung des Kaliumstroms I_Kur, der nur im Vorhof vorkommt, und I_to, der aufgrund der kürzeren Aktionspotentiale eine relativ gesehen stärkere Auswirkung auf die Refraktärzeiten im Vorhof hat. Des Weiteren hemmt Vernakalant frequenz- und spannungsabhängig Natriumströme (I_Na). Die schnellen atrialen Aktionspotentiale bei Vorhofflimmern reagieren daher besonders gut auf Vernakalant, was sich klinisch in einer Konversionsrate von über 50 % bei weniger als 7 Tage bestehendem Vorhofflimmern zeigt. Eine Dosisanpassung von Vernakalant aufgrund von Alter, Geschlecht, Organinsuffizienzen oder Ko-Medikation scheint nicht erforderlich zu sein. Noch sind die Patientenzahlen in den durchgeführten Studien zu klein, um eine Aussage über das kardiale Nebenwirkungspotential von Vernakalant zu treffen. Die Kombination aus einem Trend zu Arrhythmogenität und noch geringer Erfahrung mit dieser neuen Substanz gebietet allerdings große Vorsicht auch nach Markteinführung.

Abstract

Vernakalant is a promising novel antiarrhythmic intravenous drug for the rapid conversion of atrial fibrillation to sinus rhythm. It blocks several ion currents important in cardiac action potential including IKr. Its difference to traditional antiarrhythmic drugs is a preferential effect on the atria, achieved by an inhibition of repolarizing potassium ion currents I_Kur, which is atrial-specific, and I_to, predominantly affecting atrial repolarization, as there is little atrial plateau potential. Furthermore vernakalant blocks frequency- and voltage-dependent sodium ion currents (I_Na). Thus rapid action potentials in atrial fibrillation are particularly targeted by vernakalant: this leads to a conversion rate to sinus rhythm in about 50 % of recent-onset attacks (less than 7 days) of atrial fibrillation. Age, gender, organ function and concomitant medication seem to have no clinically significant influence on the pharmacokinetics of vernakalant. The number of patients included in the studies is still too small to provide a definitive answer on its cardiac toxicity. However, a demonstrated tendency towards proarrhythmia and little experience with this new drug demands precaution even after it has been officially approved.

Schlüsselwörter

Vorhofflimmern - vorhofselektive Antiarrhythmika - ultraschneller verzögerter Gleichrichter - I_Kur - Vernakalant

Keywords

atrial fibrillation - atrial selective antiarrhythmic drugs - ultrarapid delayed rectifier - I_Kur - Vernakalant

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