Advances in Arrhythmia and Electrophysiology New Pharmacological Agents for Arrhythmias

Despite advances in catheter ablation techniques and device-based therapies for cardiac arrhythmias, antiarrhythmic drugs remain essential components of any comprehensive therapeutic strategy. Antiarrhythmic drug therapy, however, has been limited by both incomplete efficacy and a substantial potential for cardiac and extracardiac toxicity. As a result, only a few new antiarrhythmic agents have successfully completed clinical development programs and reached routine clinical usage over the past 20 years. Antiarrhythmic drugs may be indicated for ventricular tachycardia, sudden death prevention, or specific types of supraventricular arrhythmia. Implantable cardioverterdefibrillator (ICD) therapy has evolved as the primary treatment for most life-threatening ventricular arrhythmias, and antiarrhythmic drugs for these rhythms are currently mostly used either as acute interventions or as adjuncts to chronic ICD therapy. Although numerous trials have evaluated the effect of antiarrhythmic drugs to decrease ICD shocks or therapies, such data have yet to provide the sole basis for approval for any new agent. At the same time, drug therapy for atrial arrhythmias is often limited by the drug’s simultaneous effects on the ventricles, which has led to efforts to identify ionic channel targets specific to or preferentially located in the atria. The sustained outward K current (IKur, encoded by the Kv 1.5 subunit), the acetylcholine-activated outward K current (IKAch), and both peak and late atrial Na currents have therefore become potential targets for antiarrhythmic drug developers.1–4 Another approach has been to seek agents that synergistically affect multiple channels simultaneously, resulting in a net beneficial effect while minimizing toxicity. Other nontraditional targets for drug therapy that do not directly involve ion channels have also emerged as our understanding of the mechanisms of arrhythmias has improved. As a result, several new compounds are now at or near completion of phase 3 clinical trials, and other promising agents are in earlier phases of clinical testing. This review will discuss the properties and potential future uses of several of these agents, concentrating on those with promising clinical data.