Late Sodium Current Inhibition: The Most Promising Antiarrhythmic Principle in the Near Future?

G.      Frommeyer; P.      Milberg; L.S.      Maier; L.      Eckardt

Abstract

Ranolazine has primarily been developed and so far approved as an antianginal drug. However, it also has potentially interesting and relevant antiarrhythmic properties. Its antiarrhythmic effects are mainly based on the blockade of sodium currents, in particular of the late sodium current. Experimental and clinical studies have revealed an antiarrhythmic effect of ranolazine in atrial fibrillation as chronic or “pill in the pocket” therapy. Of note, this effect was preserved in the setting of chronic heart failure. Furthermore, an antiarrhythmic effect has also been shown in experimental models of ventricular tachyarrhythmias. In addition, prevention of ventricular tachyarrhythmias has been demonstrated in patients with structural heart disease. A few late sodium current inhibitors are evaluated for antiarrhythmic properties in experimental studies. However, randomized clinical data is not yet available for these recently developed agents and larger controlled trials are necessary before recommending ranozaline as a novel antiarrhythmic drug.

Keywords: Atrial fibrillation, late sodium current, post-repolarization refractoriness, proarrhythmia, ranolazine, ventricular fibrillation

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