Efficiency and safety of the modified protocol for cardioversion of atrial fibrillation using the antiarrhythmic drug niferidil. First results of clinical use

Abstract

Abstract Introduction Atrial fibrillation (AF) is one of the most common forms of arrhythmia. Niferidil is a new russian class III antiarrhythmic drug that has shown high efficiency in restoration of sinus rhythm (SR) in persistent AF (87%) in clinical trials that is non-inferior to direct current cardioversion. Currently, a three-stage scheme of drug administration is used (10 μg/kg – 10 μg/kg – 10 μg/kg). In a number of patients, SR restored before the end of injection of the first dose of the drug, which suggests the effectiveness of an even lower dose (5 μg/kg) of the drug, which has not been studied in clinical trials. Objective To evaluate the effectiveness and safety of the modified protocol of niferidil administration in patients with paroxysmal and persistent AF. Materials and methods This study included 100 patients with paroxysmal (n=20) and persistent AF (n=80), 53 of them were men, mean age 63±12 years. After exclusion of contraindications, all patients received niferidil according to the following scheme. The initial dose of niferidil was 5 μg/kg of body weight, if AF did not terminate after 15 minutes (min.), niferidil was additionally administered at a dose of 5 μg/kg (total dose of 10 μg/kg). If SR was not restored patients received subsequent injections of niferidil 10 μg/kg, each after 15 min. (maximal total dose of 30 μg/kg). Injections were discontinued in case of SR restoration, QTc >500 ms or proarrhythmia. All patients underwent continuous ECG monitoring within 24 hours to assess effectiveness and safety of niferidil. Results SR was restored in 94 out of 100 patients (cumulative effectiveness of niferidil in doses up to 30 μg/kg was 94%). 37% of patients restored SR after a dose of 5 μg/kg. All 20 patients with paroxysmal AF restored SR within 24 hours. Niferidil restored SR in 74 of 80 patients with persistent AF (92,5%). 26 (32,5%) of them restored SR after administration of 5 μg/kg dose, 62% – after 10 μg/kg dose and 92,5% – after 30 μg/kg dose. In none of the cases was there any development of life-threatening ventricular arrhythmias. Prolongation of the QTc >500 ms was recorded in 16 patients (16%). In all patients, prolongation of the QTc interval to the maximum values was noted within the first 6 hours from the start of drug administration. Bradyarrhythmias after SR recovery were reported in 11 patients (11%). In all cases sinus bradycardia was asymptomatic and resolved within a few minutes without any therapeutic intervention. Conclusions The modified protocol of cardioversion allows SR to be restored in a significant number of AF patients lower doses of niferidil. The drug is highly effective in the treatment of paroxysmal AF, while in many patients, SR recovery occurs after injection of lowest (5 μg/kg and 10 μg/kg) doses of the drug. Despite the prolongation of the QTc interval >500 ms in a number of patients, in none of the cases the development of Torsades de pointes observed. Funding Acknowledgement Type of funding sources: None.