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Vol. 73. Issue 12.
Pages 1082-1083 (December 2020)
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Vol. 73. Issue 12.
Pages 1082-1083 (December 2020)
Letter to the Editor
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Do we have a new drug for heart rate control in patients with permanent atrial fibrillation?
¿Hay un nuevo fármaco disponible para el control de la frecuencia cardiaca de pacientes con fibrilación auricular permanente?
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Nuria Rivas-Gándaraa,b,c,d,
Corresponding author
nrivas@vhebron.net

Corresponding author:
, Jaume Francisco-Pascuala,b,c,d
a Unidad de Arritmias, Servicio Cardiología, Hospital Universitario Vall d’Hebron, Barcelona, Spain
b Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain
c Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain
d Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Spain
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To the Editor,

We have read with great interest the article by Fontenla et al.1 describing the design of the BRAKE-AF project, which will analyze the safety and efficacy of ivabradine for heart rate control in patients with permanent atrial fibrillation.

Ivabradine has shown beneficial effects in patients with ischemic heart disease and in patients with heart failure and reduced ejection fraction.2 The drug has a good safety profile, as it does not affect cardiac contractility or blood pressure due to its selective If current inhibition. Until recently, the negative chronotropic effect of the drug was considered the result of its selective effect in the sinus node and, therefore, it was not recommended for heart rate control in patients with atrial fibrillation. However, recent studies have suggested that ivabradine slows atrioventricular (AV) conduction and may be beneficial in these patients.3 Fontenla et al.1 have proposed this study, as this effect is biologically plausible (the AV node does have If currents) and this hypothesis is supported by several experimental animal studies4 and small human trials.5

The BRAKE-AF project is a promising undertaking, as the therapeutic armamentarium available for heart rate control in patients with permanent atrial fibrillation is scant and insufficient in a significant percentage of patients. In fact, beta-blockers, which are the most effective drugs in this context, do not achieve adequate heart rate control in 30% of patients.6 Furthermore, calcium channel blockers are contraindicated in the presence of severe ventricular dysfunction, and digoxin has a narrow therapeutic margin and is associated with higher mortality.7 As a result, some patients require pacemaker implantation and AV node ablation to achieve adequate heart rate control.8 New drugs with negative chronotropic effects could add to current therapeutic options and may help minimize invasive treatment.

The project is based on a sound design with 2 differentiated arms: an experimental arm to analyze the effect of the drug on the action potential of the AV node and a noninferiority clinical trial. The aim of the clinical trial, which compares the efficacy of digoxin with ivabradine, is rational, as digoxin is less successful in controlling heart rate than beta-blockers or L-type calcium channel blockers. The trial has several limitations. In particular, it uses an unblinded approach, in view of the effects of digoxin on the surface electrocardiogram, and includes patients with and without ventricular dysfunction. Ivabradine could have a different effect in patients with ventricular dysfunction; therefore, based on the results of the trial, a second study could be undertaken in this subgroup.

We look forward to the publication of the results of the BRAKE-AF project to learn the therapeutic possibilities of ivabradine in this context.

References
[1]
A. Fontenla, M. Lopez-Gil, J. Tamargo-Menendez, et al.
Ivabradine for chronic heart rate control in persistent atrial fibrillation Design of the BRAKE-AF project.
Rev Esp Cardiol., 73 (2020), pp. 368-375
[2]
F. Hidalgo, F. Carrasco, J.C. Castillo, et al.
Effect of early treatment with ivabradine plus beta-blockers on long-term outcomes in patients hospitalized with systolic heart failure.
Rev Esp Cardiol., 71 (2018), pp. 1086-1088
[3]
C. Giuseppe, F. Chiara, R. Giuseppe, et al.
Addition of ivabradine to betablockers in patients with atrial fibrillation: Effects on heart rate and exercise tolerance.
Int J Cardiol., 202 (2016), pp. 73-74
[4]
R.L. Verrier, R. Bonatti, A.F.G. Silva, et al.
If inhibition in the atrioventricular node by ivabradine causes rate-dependent slowing of conduction and reduces ventricular rate during atrial fibrillation.
Heart Rhythm., 11 (2014), pp. 2288-2296
[5]
W. Wongcharoen, A. Ruttanaphol, S. Gunaparn, et al.
Ivabradine reduced ventricular rate in patients with non-paroxysmal atrial fibrillation.
Int J Cardiol., 224 (2016), pp. 252-255
[6]
B. Olshansky, L.E. Rosenfeld, A.L. Warner, et al.
The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: approaches to control rate in atrial fibrillation.
J Am Coll Cardiol., 43 (2004), pp. 1201-1208
[7]
M.P. Turakhia, P. Santangeli, W.C. Winkelmayer, et al.
Increased mortality associated with digoxin in contemporary patients with atrial fibrillation: findings from the TREAT-AF study.
J Am Coll Cardiol., 64 (2014), pp. 660-668
[8]
J. Ibáñez-Criado, A. Quesada, R. Cózar, et al.
Registro Español de Ablación con Catéter XVIII Informe Oficial de la Sección de Electrofisiología y Arritmias de la Sociedad Española de Cardiología (2018).
Rev Esp Cardiol., 72 (2019), pp. 1031-1042
Copyright © 2020. Sociedad Española de Cardiología
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