Newer antiarrhythmic agents for maintaining sinus rhythm in atrial fibrillation: simplicity or complexity?

The morbidity and mortality associated with atrial fibrillation (AF), the most frequent cardiac arrhythmia, remain substantial. The efficacy and safety of current antiarrhythmic drugs continue to be less than optimal. The development of newer antiarrhythmic drugs has recently been made possible through a greater understanding of the pathophysiology of AF and knowledge of atrial electrophysiology relative to the properties of the congeners of known antiarrhythmic agents. Highly specific atrially acting drugs are currently being explored, their major merit concerning safety. In contrast, their role may be somewhat limited in view of the electrophysiological complexity of AF as an arrhythmia. The data suggest that complex antiarrhythmic agents with a multiplicity of actions may be preferable, although currently there are few data on the precise effectiveness of atrial-specific agents in maintaining sinus rhythm in AF. It is of interest that combining antiarrhythmic and non-antiarrhythmic agents, such as anti-inflammatory or antioxidant drugs, may increase the effectiveness of antifibrillatory actions in patients with AF, although these data have been obtained in uncontrolled, small or retrospective studies. Thus, at present, it is not certain whether it is preferable to target single antiarrhythmic drugs with antiadrenergic properties or to combine ‘purely’ antiarrhythmic drugs with other drugs devoid of anti-adrenergic effects. Controlled clinical trials are required to precisely define the effectiveness of single agents vs. various combinations of agents in maintaining sinus rhythm in patients with AF.