New developments in atrial antiarrhythmic drug therapy.

Atrial fibrillation (AF) is a growing clinical problem associated with increased morbidity and mortality. Currently available antiarrhythmic drugs (AADs), although highly effective in acute cardioversion of paroxysmal AF, are generally only moderately successful in long-term maintenance of sinus rhythm. The use of AADs is often associated with an increased risk of ventricular proarrhythmia, extracardiac toxicity, and exacerbation of concomitant diseases such as heart failure. AF is commonly associated with intracardiac and extracardiac disease, which can modulate the efficacy and safety of AAD therapy. In light of the multifactorial intracardiac and extracardiac causes of AF generation, current development of anti-AF agents is focused on modulation of ion channel activity as well as on upstream therapies that reduce structural substrates. The available data indicate that multiple ion channel blockers exhibiting potent inhibition of peak I(Na) with relatively rapid unbinding kinetics, as well as inhibition of late I(Na) and I(Kr), may be preferable for the management of AF when considering both safety and efficacy.