Suppression of resistant ventricular arrhythmias by twice daily dosing with flecainide

Abstract

Flecainide acetate is a new antiarrhythmic agent whose pharmacokinetics have suggested that effective therapy could be achieved with twice daily dosing. The antiarrhythmic and electrocardiographic effects of flecainide were evaluated in 11 patients with chronic ventricular ectopic beats. Nine patients had been resistant or intolerant to at least three antiarrhythmic agents and eight had recurrent nonsustained ventricular tachycardia. The antiarrhythmic efficacy of increasing doses of flecainide was determined by comparison with results during administration of a placebo 2 days before and 3 days after increasing doses of flecainide. All 11 patients had an antiarrhythmic response with a mean 97 percent (range 88 to 100) rate of suppression of ventricular ectopic beats and mean 100 percent rate of suppression of ventricular tachycardia with a mean daily dose of 410 mg (range 200 to 600) of flecainide. Effective therapy was accompanied by lengthening of the P-R (+ 29 percent), QRS (+ 27 percent) and Q-Tc (+ 11 percent) intervals. These changes were not associated with a deterioration in exercise tolerance or a reduction in ejection fraction (0.52 ± 0.08 with placebo, 0.53 ± 0.12 with flecainide) as assessed with two dimensional echocardiography. Increasing doses of flecainide were associated with progressive prolongation of the ventricular ectopic coupling interval before suppression of ventricular ectopic beats. During the placebo washout period after multiple oral doses, the terminal (postabsorptive) phase plasma half-life of flecainide was found to range from 13 to 27 hours (mean 20.3). The minimal effective plasma levels of flecainide (resulting in greater than 90 percent suppression of ventricular etopic beats) ranged from 245 to 980 ng/ml (mean 631). Adverse effects during the inpatient evaluation were limited to blurring of vision in three patients, which resolved with smaller but still effective doses. Suppression of ventricular ectopic beats at a mean rate of 95 percent continued during outpatient therapy. During a mean of 12 months of outpatient follow-up in nine patients, regularly scheduled evaluation of ambulatory arrhythmia frequency continued to document suppression of arrhythmia. Outpatient follow-up occurred monthly for the first 6 months and every 2nd month thereafter. In three patients it was necessary to administer flecainide every 8 hours because blurring of vision occurred at the time of peak plasma levels when the drug was administered every 12 hours. Flecainide was highly effective in suppressing ventricular arrhythmias when administered twice daily.