Atrial-selective drugs for treatment of atrial fibrillation.

Atrial fibrillation (AF) is accompanied by a high risk of thromboembolic complications necessitating anticoagulation therapy. Arrhythmias have a high tendency to become persistent. Catheter ablation techniques are highly effective in the treatment of AF; however, these procedures are far too costly and time-consuming for the routine treatment of large numbers of AF patients. Moreover, many patients prefer drug treatment although conventional antiarrhythmic drugs are moderately effective and are burdened with severe cardiac and noncardiac side effects. New antifibrillatory drugs developed for the treatment of AF include multichannel blockers with a high degree of atrial selectivity. The rationale of this approach is to induce antiarrhythmic actions only in the atria without conferring proarrhythmic effects in the ventricles.Atrial selective drug action is expected with ion channel blockers targeting ion channels that are expressed predominantly in the atria, i.e., Kv1.5 (I(Kur)), or Kir 3.1 and Kir 3.4 (I(K,ACh)). Na(+) channel blockers that dissociate rapidly may exert atrial selectivity because of subtle differences in atrial and ventricular action potentials. Finally, atrial-selective targets may evolve due to disease-specific processes (e.g., rate-dependent Na(+) channel blockers, selective drugs against constitutively active I(K,ACh) channels).