ICU Management & Practice, Volume 21 - Issue 1, 2021

Evidence-Based Management of Atrial Fibrillation

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The 2020 ESC Guidelines and the addition of Landiolol


An overview of the updated guidelines for the diagnosis and management of atrial fibrillation, developed in association with the European Association for Cardio-Thoracic Surgery.


The European Society of Cardiology (ESC) provides a range of scientific and educational activities, such as the production and continuous updating of clinical practice guidelines for the diagnosis and treatment of cardiovascular diseases. In 2020, the ESC published new updated guidelines for the diagnosis and management of atrial fibrillation (AF), developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS) (Hindricks et al. 2020). 


Rate control is an integral part of AF management and is often sufficient to improve AF-related symptoms. In these guidelines, beta-blockers are recommended as first-choice drugs to control heart rate in AF patients with left ventricular ejection fraction (LVEF) ≥40% or LVEF<40% (Class I, LoE*B) (Hindricks et al. 2020). For the first time landiolol is included in these important guidelines. Landiolol is included as the only agent with a specific dose recommendation in patients with cardiac dysfunction (dosages of 1 μg/kg/min up to 10 μg/kg/min) (Hindricks et al. 2020). On the other hand, intravenous amiodarone may be considered in patients with haemodynamic instability or severely depressed LVEF, for acute control of heart rate nevertheless with a lower Class of Recommendation (Class IIb, LoE B) (Hindricks et al. 2020). 


Landiolol is a new ultra-short acting (T1/2=4min), intravenous, most β1 selective blocker, for the treatment of supraventricular tachyarrhythmias such as AF, atrial flutter (AFl) and non-compensatory sinus tachycardia (SmPC Rapibloc®). Landiolol is a new kind of β-blocker, a pure S-enantiomer molecule which offers rate control with minimal negative impact on blood pressure (Balic et al. 2018). Furthermore, landiolol has low volume distribution of 0.3 l/kg – 0.4 l/kg (SmPC Rapibloc®). This is very important because landiolol will not be stored in the tissues (DiPiro et al. 2010), thus avoiding possible toxicities (Abialbon 2019). Compared to esmolol, in experimental models, landiolol showed very high cardioselectivity (β1/β2-selectivity = 33:1 vs. 255:1) (Shibata et al. 2012). This translates to eightfold higher cardioselectivity for landiolol over esmolol. Landiolol due to the highest cardioselectivity offers minimal impact on respiratory function (Balic et al. 2018) and unveils β2-receptor-mediated coronary hyperaemia (Maman et al. 2017). In an experimental study, landiolol appeared to have a minimal effect on the refractory period of the action potential of a cardiomyocyte, in contrast to esmolol which dose-dependently shortened the refractory period. This is because landiolol does not affect Na+ and Ca2+ ion currents, resulting in a minimal affected cardiac contractility (less inotropic effect) (Shibata et al. 2012). Landiolol also has a favourable safety profile for patients with renal and hepatic comorbidities, due to inactive metabolites and hydrolysis by plasma esterases (Yokayama 2016). 


Further statements from ESC guidelines (Hindricks et al. 2020): 

  • Amiodarone can be useful as a last resort when heart rate cannot be controlled.
  • Some antiarrhythmic drugs (AADs) also have rate-limiting properties (e.g., amiodarone, dronedarone, sotalol) but generally they should be used only for rhythm control.
  • Intravenous administration of amiodarone may lead to a further decrease in blood pressure in haemodynamic instable patients.
  • The “rhythm control strategy” refers to attempts to restore and maintain sinus rhythm, and may engage a combination of treatment approaches, along with an adequate rate control.

Landiolol is the first innovative drug for acute heart rate control in cardiovascular risk patients which significantly improves the treatments options.


Landiolol is marketed by AMOMED (member of AOP Orphan Group). For more information regarding the product, please visit www.amomed.com.


*LoE: Level of Evidence


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References:

Abialbon P (2019) Drug Distribution. In: Raj G., Raveendran R. (eds) Introduction to Basics of Pharmacology and Toxicology. Springer, Singapore. doi.org/10.1007/978-981-32-9779-1_6


Balic et al. (2018) Landiolol for managing post-operative atrial fibrillation. European Heart Journal Supplements, 20(Supp A):A10–A14. doi:10.1093/eurheartj/sux036


DiPiro JT et al. (2010) Concepts in Clinical Pharmacokinetics. Lesson 1; Introduction to Pharmacokinetics and Pharmacodynamics; pp: 1-19.


Hindricks et al. (2020) 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). European Heart Journal, 42(5):373-498, doi.org/10.1093/eurheartj/ehaa612


Maman et al. (2017) Beta-1 vs. beta-2 adrenergic control of coronary blood flow during isometric handgrip exercise in humans. J Appl Physiol., 1;123(2):337-343. doi: 10.1152/japplphysiol.00106.2017 


Shibata et al. (2012) Direct Effects of Esmolol and Landiolol on Cardiac Function, Coronary Vasoactivity, and Ventricular Electrophysiology in Guinea-Pig Hearts. J Pharmacol Sci, 118, 255 – 265


Summary of Rapibloc® Product Characteristics, current version.


Yokoyama H. (2016) Stabilization in Off-Pump Coronary Artery Bypass. Springer Tokyo Heidelberg New York Dordrecht London © Springer Japan





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