Antiarrhythmic drug therapy for congestive heart failure with focus on moricizine

Abstract

Many patients who have serious ventricular arrhythmia requiring antiarrhythmic drug therapy have congestive heart failure (CHF). However, the pharmacokinetic and pharmacodynamic properties of the antiarrhythmic drugs are altered in the presence of CHF. It has been reported that some adverse effects, primarily aggravation of arrhythmia and CHF occur more frequently in patients with a history of left ventricular (LV) dysfunction. Moreover, antiarrhythmic drugs are less effective in patients with a history of CHF and a reduced LV ejection fraction (LVEF). Moricizine, a new antiarrhythmic drug, has been undergoing clinical trials for over 13 years in the United States. The data base involving 1,072 patients was analyzed to establish the effect of this agent in patients with CHF. The presence of CHF does not alter the absorption, half-life and clearance of moricizine. The incidence of CHF exacerbation definitely related to moricizine was low (2%) and occurred primarily in patients with a history of CHF. Aggravation of arrhythmia and conduction abnormalities also occurred more often in patients with prior CHF. However, the incidence of all other adverse effects involving other organ systems was the same in patients with and without CHF and was also unrelated to the baseline LVEF. The effect of moricizine for suppressing spontaneously occurring ventricular ectopy was also similar in patients with and without CHF and was independent of LVEF. However, the drug is less effective in preventing sustained ventricular arrhythmia in patients with CHF.