Newer Antiarrhythmic Agents for Atrial Fibrillation: Shall we Eventually do away with Proarrhythmia?

Abstract

Despite advances in drug therapy for the treatment of atrial fibrillation (AF), there continues to be a need for antiarrhythmic agents that have improved safety and efficacy profile. Unfortunately, drugs that block the potassium channels or are multichannel blockers, although they may be effective antiarrhythmics, they delay repolarization and thus they confer a proarrhythmic effect by inducing torsade de pointes, a potentially lethal ventricular arrhythmia. Most newer antiarrhythmic drugs are potassium channel blockers and this limits their usefulness. A less toxic agent compared to amiodarone, the noniodinated analogue of amiodarone (dronedarone) is being investigated; however, it appears already unsafe in patients with heart failure. Future antiarrhythmic agents will probably be atrial-selective blocking agents without affecting repolarization in the ventricular myocardium and thus avoid ventricular proarrhythmia with its attendant life-threatening consequences. I N T R O D U C T I O N Despite advances in drug therapy for the treatment of atrial fibrillation (AF), there continues to be a need for antiarrhythmic agents that have improved safety and efficacy profile. The wavelength in the atrium plays a critical role in AF. The two fundamental mechanisms of antiarrhythmic drugs in terminating AF include slowing of conduction and lengthening of repolarization and refractoriness. In the wake of the CAST trial demonstrating the proarrhythmic properties of agents with selectivity for sodium channels, when used as antiarrhythmic drugs in patients with significant underlying structural heart disease, attention switched to drugs inhibiting potassium channels. They terminate and/or prevent AF by lengthening action potential duration and the effective refractory period. Unfortunately, drugs that delay repolarization can induce polymorphic ventricular tachycardia in the form of torsade de pointes, a potentially lethal proarrhythmic effect. RevIew 2 Department of Cardiology, Evagelismos General Hospital of Athens, Athens, Greece HOSPITAL CHRONICLES 2008, 3(1): 25–28 Correspondence to: Anthony Sideris, MD 2nd Department of Cardiology Evagelismos Hospital Athens, Greece E-mail: asideris@hol.gr Key wORDS: antiarrhythmic agents; atrial fibrillation; proarrhythmia; torsade de pointes; atrial selective