Prevention of symptomatic recurrences of paroxysmal atrial fibrillation in patients initially tolerating antiarrhythmic therapy. A multicenter, double-blind, crossover study of flecainide and placebo with transtelephonic monitoring. Flecainide Supraventricular Tachycardia Study Group.

Anderson, Jeffrey L.; Gilbert, Edward M.; Alpert, Barry L.; Henthorn, Richard W.; Waldo, Albert L.; Bhandari, Anil K.; Hawkinson, R W; Pritchett, Edward L.C.

doi:10.1161/01.cir.80.6.1557

Cited by 258 publications

(72 citation statements)

References 42 publications

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“…Flecainide initially showed promise as an antiarrhythmic agent against both ventricular [59] and atrial arrhythmias [60] . Because a predomi- [36] .…”

Section: Flecainidementioning

confidence: 99%

Targeting ryanodine receptors for anti-arrhythmic therapy

McCauley

Wehrens

2011

Acta Pharmacol Sin

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Antiarrhythmic drugs are a group of pharmaceuticals that suppress or prevent abnormal heart rhythms, which are often associated with substantial morbidity and mortality. Current antiarrhythmic drugs that typically target plasma membrane ion channels have limited clinical success and in some cases have been described as being pro-arrhythmic. However, recent studies suggest that pathological release of calcium (Ca 2+ ) from the sarcoplasmic reticulum via cardiac ryanodine receptors (RyR2) could represent a promising target for antiarrhythmic therapy. Diastolic SR Ca 2+ release has been linked to arrhythmogenesis in both the inherited arrhythmia syndrome 'catecholaminergic polymorphic ventricular tachycardia' and acquired forms of heart disease (eg, atrial fi brillation, heart failure). Several classes of pharmaceuticals have been shown to reduce abnormal RyR2 activity and may confer protection against triggered arrhythmias through reduction of SR Ca 2+ leak. In this review, we will evaluate the current pharmacological methods for stabilizing RyR2 and suggest treatment modalities based on current evidence of molecular mechanisms.

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“…Flecainide initially showed promise as an antiarrhythmic agent against both ventricular [59] and atrial arrhythmias [60] . Because a predomi- [36] .…”

Section: Flecainidementioning

confidence: 99%

Targeting ryanodine receptors for anti-arrhythmic therapy

McCauley

Wehrens

2011

Acta Pharmacol Sin

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“…9 A number of studies have demonstrated that flecainide and propafenone are effective for preventing recurrence of AF. [10][11][12] The effectiveness of flecainide is comparable to quinidine, but with fewer side effects. Propafenone is more effective at maintaining sinus rhythm than quinidine, and is as effective as sotalol.…”

Section: Rhythm Control In Atrial Fibrillationmentioning

confidence: 99%

Modern management of atrial fibrillation

2007

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-Atrial fibrillation (AF) continues to offer a management challenge to physicians. The incidence of this arrhythmia is rising and the cost to the healthcare system is vast. Much of this health burden relates to the high risk of stroke and thromboembolism associated with AF. This review covers common treatment strategies employed in AF management, discusses relevant drug therapy and the role of electrophysiology or surgery.KEY WORDS: antiarrhythmic drugs, atrial fibrillation, stroke, thromboembolic prophylaxis IntroductionAs the most common arrhythmia encountered in clinical practice and with rapidly evolving treatment strategies, atrial fibrillation (AF) continues to offer a management challenge to the physician. This emerging health epidemic is reflected by AF now consuming approximately 1% of NHS expenditure.Cross-sectional studies have shown that the prevalence and incidence of AF continues to surge, correlating in particular with the advancing age of Western populations. In those over 65, approximately 5% have AF, while in those aged over 80 years, this figure rises to 10%.This review focuses on management of AF with reference to the National Institute for Health and Clinical Excellence (NICE) evidence-based clinical guidelines published in June 2006. 1 In addition, the American College of Cardiology/American Heart Association/European Society of Cardiology consensus guidelines for the management of patients with AF have also now been updated. 2 Risk factors for atrial fibrillationMany risk factors for AF have been identified. As well as advancing age, there is a strong link with hypertension, ischaemic heart disease, structural/functional heart disease, valvular heart disease and hyperadrenergic states (such as thyrotoxicosis or illicit drug use), to name but a few. In some patients, alcohol excess may provide an adequate trigger for acute AF.In fact, the array of associations with AF is enormous (Box 1) and in part explains why a detailed knowledge of this condition is essential for both the generalist and specialist alike; not only will cardiologists frequently encounter AF, but so will colleagues in other specialties. Symptoms and presentationThe incidental finding of asymptomatic AF remains relatively common, often detected for example during preoperative assessment. Increasingly, though, AF is diagnosed during investigation for symptoms such as palpitations, dyspnoea, dizziness or syncope. This list is by no means exhaustive and it is increasingly recognised that AF contributes to or exacerbates numerous complaints, including lethargy, fatigue and anxiety. Additionally, it is important to remember that other conductive or atrioventricular nodal diseases may coexist with AF and in those who complain of syncopal episodes this should be considered as a co-diagnosis. Box 2 illustrates the most common symptoms reported in association with AF. ClassificationThe classification of AF has been through a period of change. Most are now agreed on a clinical classification system, based on the temporal pat...

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“…The Flecainide NDA to the Food and Drug Administration established efficacy in patients without structural heart disease by showing that the time to a first symptomatic episode of paroxysmal atrial fibrillation was increased (4 to 5 fold) as documented by patient activated trans-telephonic recordings. 87 A similar approach was used successfully in the propafenone NDA. In both cases, in contrast to the results of CAST, 88 there was no substantial adverse effect on survival.…”

Section: Clinical Trial Strategies For Atrial Fibrillationmentioning

confidence: 99%

The Search for Novel Antiarrhythmic Strategies

Gambit¹

1998

Jpn Circ J

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he first 2 meetings of the Sicilian Gambit focused on a pathophysiologic approach to evaluate antiarrhythmic drugs in light of the electrophysiologic mechanisms for cardiac arrhythmias; 1,2 on the extent to which this approach was effective in identifying the most appropriate therapy for clinical arrhythmias; and on areas where further information was needed to provide rational directions for therapy. 3 The stimulus for the third Sicilian Gambit meeting (the subject of this report) was continued concern over the future of antiarrhythmic drug therapy, based on (1) the increased mortality reported with d-sotalol in the SWORD trial; 4 (2) the failure of amiodarone to reduce all-cause mortality in CAMIAT 5 , EMIAT 6 and CHF-STAT 7 ; and (3) the extent to which international differences in perceived needs and guidelines for drug development might reduce enthusiasm for drug discovery. Participating in the meeting were basic and clinical scientists, investigators involved in drug trials and representatives of regulatory and funding agencies.In the following pages we emphasize that (1) traditional modalities of antiarrhythmic drug development have reached a near-impasse; (2) new perspectives should, nonetheless, lead to novel antiarrhythmic approaches; (3) information derived from molecular technology should facilitate the identification of specific targets for pharmacologic intervention; (4) at least one condition, congenital long QT syndrome, may soon represent "proof of concept" of the linkage between molecular biology and novel treatment strategies; (5) common arrhythmias like atrial fibrillation and ventricular tachycardia and fibrillation may be amenable to a similar approach; and (6) new thinking on development of novel compounds must be complemented by innovative decisions in clinical trials. We stress, as well, that a major market for antiarrhythmic drug therapy still exists: the frequency of lethal ventricular tachyarrhythmias as well as of atrial fibrillation is such that therapies having widespread applicability at modest cost must be sought. RationaleEarly approaches to antiarrhythmic drug development involved the serendipitous identification of antiarrhythmic actions of natural compounds such as cinchona 8 or compounds synthesized for other applications such as procaine. 9 This was followed by synthesis of derivative molecules (respectively, quinidine 10 and procainamide 11 ) and their testing in animal models and in human subjects. Identification of a perceived benefit in human subjects (eg, suppression of ventricular premature depolarizations) could lead to a search for related molecules the effects of which might be more sustained, less toxic and/or more potent, or with properties that might be modified advantageously. These molecules also were tested in animal models for their antiarrhythmic efficacy and toxicity and, if they passed muster, were tested in patients. Shortcomings of this approach are that molecules thus identified tend to incorporate not only the potential benefits of the so-called paren...

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Prevention of symptomatic recurrences of paroxysmal atrial fibrillation in patients initially tolerating antiarrhythmic therapy. A multicenter, double-blind, crossover study of flecainide and placebo with transtelephonic monitoring. Flecainide Supraventricular Tachycardia Study Group.

Cited by 258 publications

References 42 publications

Targeting ryanodine receptors for anti-arrhythmic therapy

Targeting ryanodine receptors for anti-arrhythmic therapy

Modern management of atrial fibrillation

The Search for Novel Antiarrhythmic Strategies

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