CYP450 2D6 Genotype and Flecainide Efficacy in the Treatment of Patients with Lone Atrial Fibrillation-A Pilot Study*

BACkgRound Cytochrome P450 2D6 (CYP2D6) has been linked to one of four phenotypes: a) ultra-rapid metabolizers (UM), with multiple gene copies; b) extensive metabolizers (EM), with a single wild type gene copy, considered normal; c) intermediate metabolizers (IM), with decreased enzymatic activity; and d) poor metabolizers (PM) with no detectable enzymatic activity. By altering the drug dose-plasma concentration relationship, these differences may lead to severe toxicity and/or therapeutic failure. oBjeCTiveS The aim of this study was to determine the correlation between CYP2D6 polymorphisms and both efficacy and magnitude of adverse reactions of flecainide, a class IC antiarrhythmic agent. MeThodS Patients with lone atrial fibrillation (AF) were enrolled in a 2-groups prospective study: patients started on flecainide at the initial visit, then were followed up at 3 and 6 months intervals (group 1) or exhibited AF recurrences on flecainide, defined as treatment failure (group 2). Data about recurrence of AF, side effects, and demographics were collected. Genotyping was performed using AmpliChip CYP450. ReSulTS A total of 26 lone AF patients were enrolled (12 in group 1, and 14 in group 2). The mean age was 47± 10.8 years and 56.2 ± 10.8 years respectively. Among the analyzed phenotypes, the following distribution was found: 1/26 (3.8%) UM, 19/26 (73%) EM, 5/26 (19%) IM, 1/26 (3.8%) PM. ConCluSionS In this small series of patients with lone atrial fibrillation, most patients were found to be extensive metabolizers of flecainide. There was no statistically significant correlation between the patients’ genotype and flecainide efficacy / side effects. i n T R o d u C T i o n Flecainide is a sodium channel blocker from the class IC group in the VaughanWilliams classification of antiarrhythmic drugs. Flecainide is metabolized by cytooRiginAl ARTiCle Arrhythmia Service, Laboratory Department, Emergency Room Department, Assaf Harofeh Medical Center, Zrifin, and Sackler School of Medicine, TelAviv and College of Management, RishonLe-Zion, Israel and Mount Sinai School of Medicine, NewYork, USA HOSPITAL CHRONICLES 2012, 7(4): 229–233 Correspondence to: Therese Fuchs, MD, Arrhythmia Service, Assaf Harofeh Medical Center, Zerifin, Israel; Tel: 972-3-616-4042 / Fax: 972-77-328-0001 / Cell: 057-734-5908; e-mail: therese@fuchs.org Manuscript received May 21, 2012; Revised manuscript received July 15, 2012; Accepted August 19, 2012 key WoRdS: CYP450 2D6 genotype; flecainide; atrial fibrillation; antiarrhythmic drugs AbbreviAtions AF = atrial fibrillation CYPP450 2D6 = cytochrome P450 2D6 EM = extensive metabolizers IM = intermediate metabolizers PM = poor metabolizers UM = ultra-rapid metabolizers * Clinical Trials.gov number: NCT00945867; Conflict of interest: none declared