CYP450 2D6 Genotype and Flecainide Efficacy in the Treatment of Patients with Lone Atrial Fibrillation
Background: 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 (IM) metabolizer, 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-arm prospective study: patients started on flecainide at the initial visit, then were followed up at 3 and 6 months intervals (arm 1) or exhibited AF recurrences on flecainide, defined as treatment failure (arm 2). Data about recurrence of AF, side effects, and demographics were collected. Genotyping was performed using AmpliChipTM CYP450.
Results: A total of 26 lone AF patients were enrolled (12 in arm 1, and 14 in arm 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.
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