Atrial-selective pharmacological therapy for atrial fibrillation: hype or hope?

Abstract

Rhythm control remains of therapeutic value for many atrial fibrillation patients despite no evidence of survival benefit. This lack of benefit may relate to side effects of conventional antiarrhythmic drugs. The introduction of novel agents was a logical consequence. Novel antiarrhythmics are currently being evaluated in preclinical or clinical studies. Among recently developed drugs, some affect one or more atrial targets, including IKur, IKACh, INa or ISAC, allowing them to act selectively on atria over ventricles. Some drugs that exhibit atrial selectivity have not been successful in preliminary studies. Block of a single atrial-specific target may be insufficient for atrial fibrillation termination and prevention, and multichannel-blocking properties may be a useful alternate approach. Drugs such as vernakalant or ranolazine inhibit multiple channels but display effective and atrial-selective actions. Furthermore, dronedarone, a prototypic multichannel blocker with additional effects on ventricular myocardium, has proven well tolerated and effective in the treatment of atrial fibrillation and may even reduce cardiovascular mortality. Efforts to develop atrial-selective antiarrhythmics are bearing fruit, but such compounds will need to exhibit equal or superior safety and efficacy compared with multichannel blockers such as dronedarone for atrial fibrillation suppression in order to prove their worth. It is still too early to tell whether atrial selectiveness is just hype or truly a hope for antiarrhythmic drug treatment of atrial fibrillation.