Use of Flecainide for the Treatment of Atrial Fibrillation

Abstract

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with substantial morbidity and impairment of quality of life. Restoration and maintenance of normal sinus rhythm is a desirable goal for many patients with AF; however, this strategy is limited by the relatively small number of antiarrhythmic drugs (AADs) available for AF rhythm control. Although it is recommended in current medical guidelines as first-line therapy for patients without structural heart disease, the use of flecainide has been curtailed since the completion of the Cardiac Arrhythmia Suppression Trial. In clinical trials and real-world use, flecainide has proven to be more effective than other AADs for the acute termination of recent onset AF. Flecainide is also moderately effective and, with the exception of amiodarone, equivalent to other AADs for the chronic suppression of paroxysmal and persistent AF. In patients without structural heart disease, flecainide has been demonstrated to be safe and well tolerated relative to other AADs. Despite this favorable profile, flecainide is underutilized, likely due to a perceived risk of ventricular proarrhythmia, a concern that has not been borne out in patients without underlying structural heart disease. Guidelines for administration and use of flecainide are summarized in this review.

Development and optimization of an in vivo electrocardiogram recording method and analysis program for adult zebrafish

“…Upon increasing our overall sample size, we recapitulated these results and observed a significant effect on QT interval despite reducing the dosing time to 15 min. These observations agree with our expectations based on the effect of FA on human cardiac electrophysiology and are consistent with the expected activity of a class Ic anti-arrhythmia drug ( Echt and Ruskin, 2020 ). Within the 15 min dosing recording session, several FA-dosed fish suffered from conduction blocks.…”

“…The class I anti-arrhythmic drug, FA, is used to treat atrial fibrillation and tachyarrhythmias in humans and is known to increase cardiac electrophysiological parameters (PR, QRS and QT) ( Echt and Ruskin, 2020 ). Previous research showed that FA treatment affected embryonic zebrafish cardiac electrophysiology ( Chopra et al, 2010 ).…”

Determinants of atrial fibrillation after cardiac surgery

“…The previous use of flecainide (OR: 2.43) and pre-and intraprocedural AF (OR 3.81) also predicted additional need for ablation [17]. Flecainide is an antiarrhythmic medicine that is used to treat irregular heartbeats and has been found to be particularly effective in the treatment of Atrial fibrillation [22]. Using this evidence, it should be considered that any flecainide course of treatment should be stopped at least 5 halflives prior to cardiac surgery or procedure [17], particularly ablation, to minimise the risk of POAF occurring.…”

Flecainide Paradoxically Activates Cardiac Ryanodine Receptor Channels under Low Activity Conditions: A Potential Pro-Arrhythmic Action

“…This indirect, RyR2-mediated effect may be the basis for the recent use of flecainide monotherapy in human CPVT, although here individuals are usually heterozygotic and thus flecainide could be acting on both WT and mutant RyR2 [34][35][36]. Flecainide's direct pro-arrhythmic actions may continue to reinforce the contra-indication of its use with structural heart disease [16,37], which has been attributed to its direct Nav1.5 inhibitory effect and would be exacerbated by the RyR2 activation reported here. The findings together are consistent with RyR2 being a large molecule influenced by multiple activation and inhibition sites potentially targeted by flecainide and variously located in RyR2's peripheral and central cytoplasmic and luminal domains all converging on gating mechanisms near the channel pore.…”