Do we need pharmacological therapy for atrial fibrillation in the ablation era?

Management of atrial fibrillation (AF) remains one of the most difficult problems of modern cardiology. Pharmacological antiarrhythmic therapy is used both for termination of episodes of AF and for prevention of AF recurrences. Recently, major trials have compared the strategy of maintenance of sinus rhythm, called rhythm control, with the strategy of heart rate control during AF and found that the rhythm control strategy was not superior to rate control in terms of mortality. Although subsequent analysis identified rhythm control as a factor of improved survival, these large trials have markedly influenced the management of AF. One of the hypotheses explaining the non-superiority of the rhythm control strategy was that the benefit of sinus rhythm was offset by the side effects of antiarrhythmic agents. As a consequence, attention was directed to non-pharmacological therapies, particularly to catheter ablation of the trigger or/and the atrial substrate using radiofrequency current or cryothermia. However, despite the reported good results of various types of interventions in the hands of highly qualified teams, catheter ablation cannot be applied to all patients with AF or to all types of AF. Furthermore, catheter ablation of AF requires sophisticated electrophysiologic laboratories equipped with expensive imaging techniques and a well-trained staff that cannot be available in sufficient number to cover the growing epidemic of AF with acceptable efficacy and safety even in rich countries. Therefore, there is still a need for pharmacological therapy aimed at the prevention of AF recurrences for the majority of AF patients. So far, attempts to provide the physician with efficient antiarrhythmic agents having a good safety profile have not been successful. However, recent research resulted in promising new approaches including prevention of AF using converting enzyme inhibitors or angiotensin 2 receptor blockers, new antiarrhythmic agents with multichannel effects such as dronedarone and tedisamil and atrial specific agents that theoretically should have no ventricular proarrhythmic effect as they target specific atrial channels such as I(KAch) and I(Kur) which are absent at the ventricular level. Other possible mechanisms of AF that represent potential targets, such as modification of stretch-activated ion channels, intervention of altered connexin expression and altered gap-junctional conductance, are currently investigated.