Twenty-five years in the making: flecainide is safe and effective for the management of atrial fibrillation

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Abstract

Atrial fibrillation (AF) is the most common arrhythmia in clinical practise and its prevalence is increasing. Over the last 25 years, flecainide has been used extensively worldwide, and its capacity to reduce AF symptoms and provide long-term restoration of sinus rhythm (SR) has been well documented. The increased mortality seen in patients treated with flecainide in the Cardiac Arrhythmia Suppression Trial (CAST) study, published in 1991, still deters many clinicians from using flecainide, denying many new AF patients a valuable treatment option. There is now a body of evidence that clearly demonstrates that flecainide has a favourable safety profile in AF patients without significant left ventricular disease or coronary heart disease. As a result of this evidence, flecainide is now recommended as one of the first-line treatment options for restoring and maintaining SR in patients with AF under current treatment guidelines. The objective of this article is to review the literature pertaining to the pharmacological characteristics, safety and efficacy of flecainide, and to place this drug in the context of current therapeutic management strategies for AF.

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Most cited references 118

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A comparison of rate control and rhythm control in patients with atrial fibrillation.

D Wyse, A Waldo, J Dimarco … (2002)

There are two approaches to the treatment of atrial fibrillation: one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm, and the other is the use of rate-controlling drugs, allowing atrial fibrillation to persist. In both approaches, the use of anticoagulant drugs is recommended. We conducted a randomized, multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death. The primary end point was overall mortality. A total of 4060 patients (mean [+/-SD] age, 69.7+/-9.0 years) were enrolled in the study; 70.8 percent had a history of hypertension, and 38.2 percent had coronary artery disease. Of the 3311 patients with echocardiograms, the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent. There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy (mortality at five years, 23.8 percent and 21.3 percent, respectively; hazard ratio, 1.15 [95 percent confidence interval, 0.99 to 1.34]; P=0.08). More patients in the rhythm-control group than in the rate-control group were hospitalized, and there were more adverse drug effects in the rhythm-control group as well. In both groups, the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic. Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy, and there are potential advantages, such as a lower risk of adverse drug effects, with the rate-control strategy. Anticoagulation should be continued in this group of high-risk patients. Copyright 2002 Massachusetts Medical Society

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Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats.

M. C. E. F. Wijffels, C Kirchhof, R Dorland … (1995)

In this study we tested the hypothesis that atrial fibrillation (AF) causes electrophysiological changes of the atrial myocardium which might explain the progressive nature of the arrhythmia. Twelve goats were chronically instrumented with multiple electrodes sutured to the epicardium of both atria. Two to 3 Weeks after implantation, the animals were connected to a fibrillation pacemaker which artificially maintained AF. Whereas during control episodes of AF were short lasting (6 +/- 3 seconds), artificial maintenance of AF resulted in a progressive increase in the duration of AF to become sustained (> 24 hours) after 7.1 +/- 4.8 days (10 of 11 goats). During the first 24 hours of AF the median fibrillation interval shortened from 145 +/- 18 to 108 +/- 8 ms and the inducibility of AF by a single premature stimulus increased from 24% to 76%. The atrial effective refractory period (AERP) shortened from 146 +/- 19 to 95 +/- 20 ms (-35%) (S1S1, 400 ms). At high pacing rates the shortening was less (-12%), pointing to a reversion of the normal adaptation of the AERP to heart rate. In 5 goats, after 2 to 4 weeks of AF, sinus rhythm was restored and all electrophysiological changes were found to be reversible within 1 week. Artificial maintenance of AF leads to a marked shortening of AERP, a reversion of its physiological rate adaptation, and an increase in rate, inducibility and stability of AF. All these changes were completely reversible within 1 week of sinus rhythm.

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A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation.

Isabelle Van Gelder, Vincent Hagens, Hans A. Bosker … (2002)

Maintenance of sinus rhythm is the main therapeutic goal in patients with atrial fibrillation. However, recurrences of atrial fibrillation and side effects of antiarrhythmic drugs offset the benefits of sinus rhythm. We hypothesized that ventricular rate control is not inferior to the maintenance of sinus rhythm for the treatment of atrial fibrillation. We randomly assigned 522 patients who had persistent atrial fibrillation after a previous electrical cardioversion to receive treatment aimed at rate control or rhythm control. Patients in the rate-control group received oral anticoagulant drugs and rate-slowing medication. Patients in the rhythm-control group underwent serial cardioversions and received antiarrhythmic drugs and oral anticoagulant drugs. The end point was a composite of death from cardiovascular causes, heart failure, thromboembolic complications, bleeding, implantation of a pacemaker, and severe adverse effects of drugs. After a mean (+/-SD) of 2.3+/-0.6 years, 39 percent of the 266 patients in the rhythm-control group had sinus rhythm, as compared with 10 percent of the 256 patients in the rate-control group. The primary end point occurred in 44 patients (17.2 percent) in the rate-control group and in 60 (22.6 percent) in the rhythm-control group. The 90 percent (two-sided) upper boundary of the absolute difference in the primary end point was 0.4 percent (the prespecified criterion for noninferiority was 10 percent or less). The distribution of the various components of the primary end point was similar in the rate-control and rhythm-control groups. Rate control is not inferior to rhythm control for the prevention of death and morbidity from cardiovascular causes and may be appropriate therapy in patients with a recurrence of persistent atrial fibrillation after electrical cardioversion. Copyright 2002 Massachusetts Medical Society

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Author and article information

Journal

Journal ID (nlm-ta): Europace

Journal ID (publisher-id): europace

Journal ID (hwp): europace

Title: Europace

Publisher: Oxford University Press

ISSN (Print): 1099-5129

ISSN (Electronic): 1532-2092

Publication date (Print): February 2011

Publication date (Electronic): 7 December 2010

Publication date PMC-release: 7 December 2010

Volume: 13

Issue: 2

Pages: 161-173

Affiliations

[1 ]Département de Cardiologie, simpleCHU de Nancy , simpleHôpital de Brabois , rue du Morvan, 54511 Vandoeuvre-lès-Nancy Cedex, France

[2 ]Clinica di Cardiologia, simpleUniversita’ Politecnica delle Marche, Torrette Hospital , 60120 Ancona, Italy

[3 ]Department of Cardiology, simpleMaastricht University Medical Center , Maastricht, The Netherlands

[4 ]Chief of Cardiology and Intensive Care Medicine, simpleSt. Vincenz Hospital , Paderborn, Germany

[5 ]Department of Pharmacology, School of Medicine, simpleUniversidad Complutense , Madrid, Spain

Author notes

[* ]Corresponding author. Tel: +33 3 83 15 32 96; fax: +33 3 83 15 38 56, Email: e.aliot@ 123456chu-nancy.fr

Article

Publisher ID: euq382

DOI: 10.1093/europace/euq382

PMC ID: 3024037

PubMed ID: 21138930

SO-VID: 37e806f6-38eb-4504-9862-3ffe0c670ee1

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Twenty-five years in the making: flecainide is safe and effective for the management of atrial fibrillation

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Most cited references 118

A comparison of rate control and rhythm control in patients with atrial fibrillation.

Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats.

A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation.

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