Dramatic reduction of ventricular tachycardia burden after dronedarone plus mexiletine treatment in a patient refractory to hybrid ablation.

Antiarrhythmic drugs are often the last resort for recurrent ventricular tachycardia refractory to catheter ablation in implantable cardioverter-defibrillator carriers. Amiodarone, alone or combined with mexiletine, is usually but not always highly effective, and its use is usually limited by systemic adverse effects. We present the case of a 62 years old man with recurrent ICD shocks due to a VT refractory to an endo-epicardial hybrid ablation. Starting of dronedarone plus mexiletine combination showed an excellent result.

Comparación de la eficacia y seguridad de flecainida y dronedarona como terapias antiarrítmicas para mantenimiento de ritmo sinusal en fibrilación auricular / Comparison of the efficacy and safety of dronedarone and flecainide as maintenance antiarrhythmic therapy for sinus rhythm in atrial fibrillation

Resumen Introducción y objetivos: Dronedarona y flecainida son antiarrítmicos de primera elección para reducir recurrencias de fibrilación auricular (FA), sin existir estudios que los comparen entre sí. Nuestro objetivo es comparar la eficacia en cuanto a prevención de recurrencias y seguridad de ambos fármacos. Métodos: Estudio retrospectivo en el que se incluyeron 123 pacientes de forma consecutiva en tratamiento con flecainida o dronedarona desde octubre de 2010 hasta febrero de 2013 por FA paroxística (76.4%) y FA persistente (23.6%). Se realizó cardioversión eléctrica en un 7.3% de los pacientes y farmacológica en un 16.3%. La mediana (rango intercuartílico) de seguimiento fue de 301 días (92-474), con una media de 2.8 revisiones por paciente. Se realizó análisis de tiempo hasta el primer evento mediante Kaplan-Meier y regresión de Cox ajustada por un índice de propensión. Resultados: De entre los 123 sujetos incluidos con FA, 71 fueron tratados con flecainida y 52 con dronedarona. Durante el seguimiento se registraron 36 recurrencias y 20 efectos adversos. Se documentaron un 36.6% de recurrencias en los pacientes tratados con flecainida en comparación con un 21% en los tratados con dronedarona (p = 0.073). En el análisis multivariante, dronedarona se mostró al menos tan eficaz como flecainida para prevenir recurrencias de FA (HR: 0.53, IC 95%: 0.20-1.44, p = 0.221) y demostró un perfil de seguridad comparable al de flecainida (HR: 0.68, IC 95%: 0.18-2.53, p = 0.566). Conclusiones: Según nuestra experiencia, dronedarona resulta al menos tan eficaz como flecainida para el mantenimiento de ritmo sinusal, con un buen perfil de tolerabilidad, a pesar de pautarse en pacientes con un perfil clínico más desfavorable.

Abstract Introduction and objectives: Dronedarone and flecainide are the first pharmacological choice to reduce recurrence of atrial fibrillation (AF); however, there are no studies comparing them. A study was performed to compare the efficacy in terms of recurrence of AF and safety of both drugs. Methods: A retrospective cohort study was conducted that included 123 consecutive patients treated with flecainide or dronedarone due to paroxysmal AF (76.4%) or persistent AF (23.6%), from October 2010 to February 2013. Electrical cardioversion was performed in 7.3% of patients and pharmacological cardioversion in 16.3%. The median (interquartile range) follow-up was 301 days (92-474) with a mean of 2.8 reviews per patient. Time to first event analysis was performed using Kaplan-Meier and Cox regression, adjusted for propensity score. Results: Of the 123 consecutive patients with AF included, 71 were on dronedarone and 52 on flecainide. During the follow-up, there were 36 AF recurrences and 20 safety events. There were recurrences in 36.6% of patients treated with flecainide, compared with 21% of those receiving dronedarone (P = .073). Dronedarone showed to be at least as effective as flecainide in preven- ting recurrence of atrial fibrillation (HR: 0.53, 95% CI: 0.20-1.44, P = .221), and demonstrated an acceptable safety profile when compared with flecainide (HR: 0.68, 95% CI: 0.18-2.53, P = .566). Conclusions: In our experience, dronedarone has been at least as effective and safe as flecainide, despite it was most frequently prescribed in patients with worse baseline risk profile.

[Comparison of the efficacy and safety of dronedarone and flecainide as maintenance antiarrhythmic therapy for sinus rhythm in atrial fibrillation]. / Comparación de la eficacia y seguridad de flecainida y dronedarona como terapias antiarrítmicas para mantenimiento de ritmo sinusal en fibrilación auricular.

INTRODUCTION AND OBJECTIVES: Dronedarone and flecainide are the first pharmacological choice to reduce recurrence of atrial fibrillation (AF); however, there are no studies comparing them. A study was performed to compare the efficacy in terms of recurrence of AF and safety of both drugs. METHODS: A retrospective cohort study was conducted that included 123 consecutive patients treated with flecainide or dronedarone due to paroxysmal AF (76.4%) or persistent AF (23.6%), from October 2010 to February 2013. Electrical cardioversion was performed in 7.3% of patients and pharmacological cardioversion in 16.3%. The median (interquartile range) follow-up was 301days (92-474) with a mean of 2.8 reviews per patient. Time to first event analysis was performed using Kaplan-Meier and Cox regression, adjusted for propensity score. RESULTS: Of the 123 consecutive patients with AF included, 71 were on dronedarone and 52 on flecainide. During the follow-up, there were 36 AF recurrences and 20 safety events. There were recurrences in 36.6% of patients treated with flecainide, compared with 21% of those receiving dronedarone (P=.073). Dronedarone showed to be at least as effective as flecainide in preventing recurrence of atrial fibrillation (HR: 0.53, 95% CI: 0.20-1.44, P=.221), and demonstrated an acceptable safety profile when compared with flecainide (HR: 0.68, 95% CI: 0.18-2.53, P=.566). CONCLUSIONS: In our experience, dronedarone has been at least as effective and safe as flecainide, despite it was most frequently prescribed in patients with worse baseline risk profile.

Principios básicos de las nuevas estrategias farmacológicas antiarrítmicas en fibrilación auricular / Basic mechanisms of the new antiarrhythmic drugs in atrial fibrillation

La fibrilación auricular (FA) es la arritmia crónica sostenida más frecuente en la población general. A pesar de los últimos avances tecnológicos y en el entendimiento de sus mecanismos, derivados de modelos experimentales, así como de los procedimientos de ablación en pacientes con FA, los fármacos antiarrítmicos siguen siendo la principal estrategia para la cardioversión y mantenimiento del ritmo sinusal. Nuevas generaciones de fármacos antiarrítmicos han llegado a la práctica clínica, y otros se encuentran en fase de experimentación. Los nuevos fármacos actúan de forma más específica sobre corrientes iónicas auriculares, y al mismo tiempo involucradas en el mantenimiento de la arritmia. Paralelamente, cada vez se da más importancia a la necesidad de actuar sobre el sustrato arritmogénico auricular y los factores que lo promueven, implicados en el mantenimiento a largo plazo de la arritmia (terapias upstream). La presente revisión tiene como objetivo exponer las actuales líneas de desarrollo en fármacos antiarrítmicos y terapias para prevención o retraso del remodelado auricular, con base a los conocimientos mecanísticos que hoy en día se involucran en el mantenimiento de la FA.

Atrial fibrillation (AF) is the most common sustained arrhythmia seen in clinical practice. Despite of new technological breakthroughs and the understanding of the mechanisms underlying AF, based on animal models and ablation procedures in patients, the antiarrhythmic drugs remain the main therapeutic strategy to restore and maintain the sinus rhythm. New antiarrhythmic drugs are already available in the clinical practice and many others are under development. The new antiarrhythmic drugs have the capability to block atrial-specific ionic currents, which are involved in the maintenance of the arrhythmia. Parallel, increasing evidence supports the use of compounds to regulate the arrhythmogenic atrial substrate involved in the long-term maintenance of the arrhythmia (upstream therapies). This article reviews the new antiarrhythmic drugs and upstream therapies, based on the current knowledge of the mechanisms involved in the maintenance of AF.