Abstract 12009: A Prospective Randomized Placebo-Controlled Crossover Trial of Flecainide for Catecholaminergic Polymorphic Ventricular Tachycardia
Introduction: Randomized clinical trials (RCTs), the gold standard to evaluate new therapies, have not been performed in Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). Up to 30% of CPVT patients have recurrent symptoms or cardiac events despite standard therapy with beta-blockers. In a mouse model flecainide was found to directly target the molecular defect in CPVT and in retrospective clinical studies patients had improved ventricular ectopy during exercise with flecainide added to beta-blockers.
Hypothesis: Flecainide + beta-blocker is superior to beta-blocker alone in CPVT.
Methods: CPVT patients were enrolled in a single blind placebo-controlled crossover RCT of flecainide added to beta-blocker. Subjects underwent a baseline exercise (Ex) test on maximally-tolerated beta-blocker dose which continued throughout the trial, then were randomized to flecainide or placebo for 3 months, followed by Ex testing. After a 1 week washout, subjects crossed over to placebo or flecainide for 3 months, followed by Ex testing. The primary endpoint of ventricular ectopy during Ex was compared between beta-blocker + flecainide vs. beta-blocker + placebo. Ex tests were scored on an ordinal scale of worst ventricular arrhythmia observed (0 = no ectopy, 1 = isolated PVC’s, 2 = bigeminy, 3 = couplets, 4 = nonsustained VT).
Results: A total of 13 subjects (7 males) at 10 centers were randomized. Median age was 16 years and baseline Ex test score was 3 (IQR 1-3.5). Ventricular ectopy during Ex was significantly reduced by flecainide (P<0.01, see Figure); there was no difference between baseline and placebo Ex score (P=0.7). Overall adverse events and serious adverse events did not differ between flecainide and placebo.
Conclusions: This placebo-controlled RCT demonstrates that flecainide + beta-blocker is superior to beta-blocker alone in reducing exercise-induced ventricular arrhythmias in CPVT.
Author Disclosures: P.J. Kannankeril: Research Grant; Significant; NIH. J.P. Moore: None. M. Cerrone: None. S.G. Priori: None. N.J. Kertesz: None. P. Ro: None. A.S. Batra: None. E.S. Kaufman: None. D.L. Fairbrother: None. E.V. Saarel: None. S.P. Etherdige: None. R.J. Kanter: None. M.P. Carboni: None. M.V. Dzurik: Consultant/Advisory Board; Modest; Biosense Webster. D. Fountain: None. H. Chen: None. E.W. Ely: None. D.M. Roden: Research Grant; Modest; NIH. B.C. Knollmann: None.
- © 2016 by American Heart Association, Inc.