Aim: to analyze the pharmacological features and updated evidence-based medicine data of Class IC antiarrhythmic drug (AAD) ethacizine compared to propafenone to optimize the choice of treatment for cardiac arrhythmias in patients without structural heart disease.

Materials and methods. According to the purpose, a search was conducted for available scientific literature with an emphasis on publications of the last 5 years. We also analyzed scientific information on scientific platforms of the European Society of Cardiology (ESC 365) and the Association of Cardiologists of Ukraine.

Results. At first glance, Class IC AADs seem to be identical in the mechanism of action, which creates certain difficulties for practicing physicians when choosing AAD of this class for the treatment of arrhythmias in each specific case. Ethacizine and propafenone were chosen for comparison as the most frequently used Class IC AADs in our country. We presented data from studies comparing the efficacy and safety of the selected AADs with an emphasis on recent studies of ethacizine, as a less well-known AAD in Europe and globally. In addition, this article includes the main design features of new studies on real-world clinical use of Class IC AADs, including use as a “pill-in-the-pocket” for restoring sinus rhythm in patients with atrial fibrillation (ETERNITY study) and comparing the efficacy of propafenone and ethacizine in maintaining sinus rhythm in patients with paroxysmal and persistent forms of atrial fibrillation.

Conclusions. Propafenone and ethacizine have significant differences in pharmacological properties, specific contraindications, drug interactions, and evidence base, which can be considered to determine the optimal agent for a particular patient. The choice of the optimal Class IC AAD will depend on the presence and type of dysautonomia of the patient.