Conversion of recent-onset atrial fibrillation by a single oral loading dose of propafenone or flecainide

Capucci, Alessandro; Boriani, Giuseppe; Botto, G; Lenzi, Tiziano; Rubino, Ida; Falcone, Camillo; Trisolino, G.; Casa, Stefano Della; Binetti, Nicola; Cavazza, Mario; Sanguinetti, M; Magnani, B

doi:10.1016/0002-9149(94)90915-6

Cited by 163 publications

(61 citation statements)

References 6 publications

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“…Twenty-five of 35 patients with new or recurrent AF converted to sinus rhythm within 6 hours of dose administration. The conversion rate we observed with ranolazine was similar to the 6 to 8 hour conversion rates previously reported with high dose oral "pill in pocket" propafenone or flecainide 10-13 and higher than the 39% placebo 8-hour conversion rate noted by Capucci et al 13 In none of our patients was ranolazine associated with any worsening of the symptoms from AF prior to conversion or did any adverse cardiovascular effects develop. Although is likely that some of these patients would have converted spontaneously without ranolazine, the high rate of conversion strongly suggests that ranolazine was instrumental in the conversion process.…”

Section: Discussionsupporting

confidence: 89%

“…Indeed it seems very likely that some would have. [10][11][12][13] But our conversion rates approximate that with class IC agents which have been proven to result in higher and more rapid conversion rates than placebo. 34 This observation serves as a useful pilot study demonstrating the feasibility of this approach.…”

Section: Limitationsmentioning

confidence: 61%

“…[4][5][6][7][8][9][10][11][12][13] Proarrhythmic concerns have limited the usefulness of anti-arrhythmic therapy in the un-monitored setting 6,8,9,14,15 as has, in some patients, bradycardic concerns and concerns about the potential transition of AF to atrial flutter with a rapid ventricular response when class IC or IA agents are used. However, in properly chosen patients, those without structural heart disease (SHD), high dose oral anti-arrhythmic agents (usually 75 to 100% of the normal daily dose of propafenone or flecainide given as a single oral dose) may effectively and safely convert 70-80% of patients with recent-onset, new or recurrent, AF [10][11][12][13] in an out-patient setting. This may be at home, unmonitored, in patients at lowest risk or in those who have previously shown both efficacy and tolerance with this approach.…”

Section: 2mentioning

confidence: 99%

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The Conversion of Paroxysmal or Initial Onset Atrial Fibrillation with Oral Ranolazine: Implications for a New "Pill-In-Pocket" Approach in Structural Heart Disease

Murdock¹,

Reiffel²,

Kaliebe³

et al. 2010

J.A.F.I.B

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Background : The "Pill-in-Pocket" (PIP) is an approach to atrial fibrillation (AF) where oral anti-arrhythmics at 75% to 100% of the normal daily dose, given as a single dose, is used to convert recent-onset AF. Pro-arrhythmic risk has limited this approach to patients without structural heart disease (SHD). Ranolazine is an anti-anginal agent, which inhibits the abnormal late Na+ channel current resulting in decreased Na+/Ca++ overload. This inhibits after-depolarizations and reduces pulmonary vein firing, which have been implicated in the initiation and propagation of AF. Ranolazine increases atrial refractoriness and has no known pro-arrhythmic affects. Ranolazine is routinely given to patients with SHD. The ability of Ranolazine to terminate AF in man has not been described but if useful could be a safer PIP agent with application in the presence or absence of SHD. We describe our experience using oral Ranolazine to convert new or recurrent AF.

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Section: Discussionsupporting

confidence: 89%

Section: Limitationsmentioning

confidence: 61%

Section: 2mentioning

confidence: 99%

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The Conversion of Paroxysmal or Initial Onset Atrial Fibrillation with Oral Ranolazine: Implications for a New "Pill-In-Pocket" Approach in Structural Heart Disease

Murdock¹,

Reiffel²,

Kaliebe³

et al. 2010

J.A.F.I.B

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“…Patients are given 200-300 mg of flecainide or 450-600 mg of propafenone to take when they enter AF to stimulate cardioversion. [64][65][66] Contraindications include AV or sinus node dysfunction, conduction system disease, QT prolongation, or Brugada syndrome. Oral flecainide and propafenone have a 94% cardioversion success rate within 6 hours in select patients in the outpatient setting.…”

Section: Medications For Conversion To Srmentioning

confidence: 99%

Atrial Fibrillation: Antiarrhythmic Therapy

Psotka¹,

Lee²

2014

Current Problems in Cardiology

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“…Such pharmacological agents should theoretically promote AF maintenance as they decrease conduction velocity by reducing I Na and shortening wavelength. Paradoxically, and contrary to these predictions, many class I substances like flecainide and propafenone are effective in converting a large proportion of recent-onset AF (Capucci et al 1994;Suttorp et al 1989). These drugs are nonselective sodium channel blockers and additionally target other ion channels (Hwang et al 2011;Voigt et al 2010) involved in the remodeling process Dobrev and Nattel 2010).…”

Section: Paradoxon Of I Na Inhibition To Terminate Afmentioning

confidence: 89%

Atrial-selective sodium channel block by dronedarone: sufficient to terminate atrial fibrillation?

Ehrlich

Dobrev

2011

Naunyn-Schmiedeberg's Arch Pharmacol

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Presently available drugs used for atrial fibrillation (AF) therapy have major limitations (moderate efficacy and increased risk of potentially life-threatening proarrhythmia), making new drug developments crucial. Novel drugs like the multichannel blocker dronedarone have the potential to convert AF to prevent AF-related stroke and to reduce cardiovascular morbidity and mortality, opening new directions for innovative antiarrhythmic options. Here we summarize mechanistic evidence for atrial-selective sodium channel block as anti-AF principle putting it into perspective to the work by Bogdan et al. 2011, which demonstrated stronger sodium current inhibition by dronedarone at depolarized potentials resulting in atrial selectivity. We also discuss pertinent facts about remodeling processes induced by and leading to AF which likely explain why pharmacological cardioversion is effective in very early stages of AF only.Atrial selectivity of sodium channel block is a novel anti-AF approach that exploits atrial-ventricular differences in sodium current properties (more negative half-inactivation in atria) and in resting membrane potential (more positive in atria leaving a greater proportion of sodium channels in the inactivated state), leading to reduced atrial current availability at any given membrane potential. Therefore inactivated-state sodium channel blockers like dronedarone preferentially suppress atrial sodium currents, especially during rapid atrial rhythms like in AF. However, dronedarone less effectively terminates AF compared to amiodarone having only a moderate overall efficacy. Much more work is needed to precisely define the contribution of atrial-selective sodium current inhibition for dronedarone's overall anti-AF efficacy.AF is an increasing health problem and is associated with substantial cardiovascular morbidity and mortality, with stroke representing the most critical complication. Presently available drugs used for therapy of AF (antiarrhythmic drugs and anticoagulants) have major limitations because of moderate efficacy and inherent risk of potentially life-threatening proarrhythmia or bleeding complications, making new drug developments crucial (Dobrev and Nattel 2010). Novel drugs like dronedarone have the potential to prevent AF-related stroke and to reduce cardiovascular morbidity and mortality ), opening a new avenue for innovative antiarrhythmic options.In January 2010 dronedarone has been approved for the treatment of nonpersistent AF in Europe. It is an antiarrhythmic compound with rate-and rhythm-controlling properties, which has been developed as a structurally related, multichannelblocking congener of amiodarone with a similarly broad spectrum of inhibitory actions on ion channels (Ehrlich and Nattel 2009). In the April issue of Naunyn-Schmiedeberg's Archive of Pharmacology, Bogdan and colleagues (2011) illustrate the mode of dronedarone action on sodium channels and identify a peculiar behavior of the substance to inhibit inactivated channels at more depolarized potentials more effe...

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Conversion of recent-onset atrial fibrillation by a single oral loading dose of propafenone or flecainide

Cited by 163 publications

References 6 publications

The Conversion of Paroxysmal or Initial Onset Atrial Fibrillation with Oral Ranolazine: Implications for a New "Pill-In-Pocket" Approach in Structural Heart Disease

The Conversion of Paroxysmal or Initial Onset Atrial Fibrillation with Oral Ranolazine: Implications for a New "Pill-In-Pocket" Approach in Structural Heart Disease

Atrial Fibrillation: Antiarrhythmic Therapy

Atrial-selective sodium channel block by dronedarone: sufficient to terminate atrial fibrillation?

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