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

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 five 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 eight patients and markedly suppressed in the other three 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 outpatient therapy with flecainide, significant suppression was present after 1 and 2 weeks of treatment (94.4% and 93.3%, respectively). Drug elimination was slow (average plasma half-life 20 hours). Ninety-five percent suppression of ventricular ectopic depolarization during dosing and 5% reappearance of arrhythmias during washout occurred with flecainide concentrations of 200-800 ng/ml. Side effects occurred in five of 11 patients, but did not require discontinuation of the drug. These results indicate that flecainide is a very effective antiarrhythmic agent that merits further clinical investigation.