Suppression of ventricular ectopic depolarizations by flecainide acetate, a new antiarrhythmic agent.

Abstract

Flecainide acetate, a new antiarrhythmic agent, was given orally to 11 hospitalized patients with chronic high-frequency ventricular ectopic depolarizations. Drug effectiveness was evaluated with a dose-ranging single-blind protocol, which included placebo control and washout periods. Twice-daily dosing (average daily dose 436 mg) completely suppressed all ventricular ectopic activity in 5 of 11 patients; average suppression in the 11 patients was 96.3%. Complex ventricular arrhythmias, which were present in all 11 patients during the placebo control period, were completely suppressed in 8 patients and markedly suppressed in the other 3 patients during flecainide therapy. Ejection fraction and velocity of circumferential fiber shortening measured by M-mode echocardiography did not change significantly during flecainide dosing. Ventricular arrhythmias returned in all patients during the placebo washout period. During subsequent out-patient therapy with flecainide, significant suppression was present after 1 and 2 wk of treatment (94.4% and 93.3%, respectively). Drug elimination was slow (average plasma half-life 20 h). Ninety-five percent suppression of ventricular ectopic depolarizations during dosing and 5% reappearance of arrhythmias during washout occurred with flecainide concentrations of 200-800 ng/ml. Side effects occurred in 5 of 11 patients, but did not require discontinuation of the drug. Flecainide is a very effective antiarrhythmic agent that merits further clinical investigation.