Combination Therapy With Dofetilide and Mexiletine for Atrial Fibrillation: Increased Efficacy and Decreased Qt Interval Prolongation

Mexiletine: Antiarrhythmic mechanisms, emerging clinical applications and mortality

“…Preliminary clinical data in AF treatment with the combination of mexiletine and dofetilide appears to be promising. In 13 patients with AF treated with dofetilide, the addition of mexiletine, due to either treatment failure or prohibitive QT prolongation, significantly delayed the recurrence of symptomatic AF 55 …”

“…In 13 patients with AF treated with dofetilide, the addition of mexiletine, due to either treatment failure or prohibitive QT prolongation, significantly delayed the recurrence of symptomatic AF. 55 The proposed mechanisms by which mexiletine may enhance the efficacy of dofetilide in AF suppression include (1) an increased ERP in atrial myocytes that are dependent on the opening of the fast sodium channels for their excitation (Figure 1): although the associated increase in ERP by mexiletine is smaller compared to Class Ic and Ia antiarrhythmic drugs; (2) reduction in triggered activity that is associated with AF initiation: secondary to a reduced influx of sodium ions into atrial myocytes and the resultant attenuation of intracellular Ca 2+ accumulation; (3) less dose reduction of dofetilide resulting from QTc prolongation: higher doses of dofetilide are associated with better efficacy (https://www.accessdata.fda.gov/drugsatfda_ docs/label/2013/020931s007lbl.pdf). It should be, however, emphasized that clinical trials are required to demonstrate whether the combination of dofetilide with mexiletine is more effective in AF suppression than dofetilide alone.…”