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Safety and Effectiveness of Pharmacologic Conversion of Atrial Fibrillation and Flutter: Results of Multicenter Trial. Part II: Assessment of Safety

https://doi.org/10.20996/1819-6446-2021-10-06

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Abstract

Aim. We aimed to assess safety and effectiveness of class III antiarrhythmic drug Refralon for conversion of atrial fibrillation (AFib) and flutter (AFl) in post-registration trial and to compare data of primary center (National medical research center in cardiology) with data of other hospitals.

Material and Methods. We performed retrospective cohort study in 727 patients (451 enrolled in primary center and 276 enrolled in other hospitals) admitted between June 24, 2014 and June 24, 2019. Refralon was administered for conversion of AFib and AFl in intense care units in escalating doses (10-30 micrograms/kg) intravenously.

Results. Conversion of AFib and AFl into sinus rhythm was achieved in 53,6% after administration of 10 mcg/kg dose, in 73% after administration of 20 mcg/kg dose and in 91,6% after administration of Refralon in dose up to 30 mcg/kg. No mortality and no major adverse cardiac events registered in our study. Asystole >3.0 sec observed in 5% (35 of 727) of patients): in 5% (24 of 451) of patients enrolled in primary center and in 4% (11 of 276) of patients enrolled in other hospitals; 95% confidence interval (CI) [-0.09; 0.113]. Asystole> 5.0 s observed in 1.7% of patients who further required non-urgent implantation of a permanent pacemaker due to manifestations of sinus node dysfunction. Cardiac conduction disturbances (exclusively sinus bradycardia) were registered in 7% (53 of 727) patients: in 8% (37 of 451) of patients enrolled in primary center and in 6% (17 of 276) of patients enrolled in other hospitals; 95% CI: [-0.1; 0.15]. Only 0.14% of patients had symptomatic sinus bradycardia that resolved after atropine injection. Ventricular arrhythmias (exclusively Torsade de pointes tachycardia in excessive QT interval prolongation) were registered in 1.7% (12 of 727) patients: in 2% (9 of 451) of patients in primary center and in 1% (3 of 276) of patients of other hospitals; 95% CI: [-0.06; 0.08]. QTc interval prolongation to values >500 ms documented in 19% (138 of 727) of patients: in 21% (95 of 451) of patients in primary center and in 16% (43 of 276) of patients in other hospitals; 95% CI: [-0.13; 0.24].

Conclusion: In post-registration multicenter trial Refralon demonstrated good safety profile in conversion of AFib and AFl. Potential risk of TdP tachycardia mandates precautions with the use of the drug. In other hospitals Refralon did not demonstrate lower safety than in primary medical center.

About the Authors

N. Yu. Mironov
National Medical Research Center of Cardiology
Russian Federation

Nikolay Yu. Mironov

Moscow, eLibrary SPIN 3542-5572



Yu. A. Yuricheva
National Medical Research Center of Cardiology
Russian Federation

Yulia A. Yuriceva

Moscow, eLibrary SPIN 8329-3595



V. V. Vlodzyanovskiy
National Medical Research Center of Cardiology
Russian Federation

Vladislav V. Vlodzyanovskiy

Moscow



S. F. Sokolov
National Medical Research Center of Cardiology
Russian Federation

Sergey F. Sokolov

Moscow, eLibrary SPIN 5551-8391



Kh. M. Dzaurova
National Medical Research Center of Cardiology
Russian Federation

Khava M. Dzaurova

Moscow



S. P. Golitsyn
National Medical Research Center of Cardiology
Russian Federation

Sergey P. Golitsyn

Moscow



Yu. V. Shubik
National Medical Research Center of Cardiology
Russian Federation

Yuriy V. Shubik

Moscow, eLibrary SPIN 6541-4328



M. V. Berman
National Medical Research Center of Cardiology
Russian Federation

Mikhail V. Berman

Moscow



M. M. Medvedev
National Medical Research Center of Cardiology
Russian Federation

Mikhail M. Medvedev

Moscow, eLibrary SPIN 4404-5907



A. E. Rivin
National Medical Research Center of Cardiology
Russian Federation

Alexey E. Rivin

Moscow, eLibrary SPIN 5218-7967



D. S. Parkhomchuk
National Medical Research Center of Cardiology
Russian Federation

Demyan S. Parkhomchuk

Moscow, eLibrary SPIN 4636-1536



A. E. Barybin
National Medical Research Center of Cardiology
Russian Federation

Artyom E. Barybin

Moscow



D. А. Balandin
National Medical Research Center of Cardiology
Russian Federation

Dmitry A. Balandin

Moscow



R. E. Batalov
National Medical Research Center of Cardiology
Russian Federation

Roman E. Batalov

Moscow, eLibrary SPIN 1371-4429



D. V. Terekhov
National Medical Research Center of Cardiology
Russian Federation

Denis S. Terekhov

Moscow, eLibrary SPIN 1638-6136



I. V. Evstifeev
National Medical Research Center of Cardiology
Russian Federation

Ivan V. Evstifeev

Moscow



I. R. Kildeev
National Medical Research Center of Cardiology
Russian Federation

Ilham R. Kildeev

Moscow



O. V. Pyataeva
National Medical Research Center of Cardiology
Russian Federation

Olga V. Pyataeva

Moscow, eLibrary SPIN 8357-9625



S. A. Zenin
National Medical Research Center of Cardiology
Russian Federation

Sergey A. Zenin

Moscow, eLibrary SPIN 4546-3790



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For citation:


Mironov N.Yu., Yuricheva Yu.A., Vlodzyanovskiy V.V., Sokolov S.F., Dzaurova K.M., Golitsyn S.P., Shubik Yu.V., Berman M.V., Medvedev M.M., Rivin A.E., Parkhomchuk D.S., Barybin A.E., Balandin D.А., Batalov R.E., Terekhov D.V., Evstifeev I.V., Kildeev I.R., Pyataeva O.V., Zenin S.A. Safety and Effectiveness of Pharmacologic Conversion of Atrial Fibrillation and Flutter: Results of Multicenter Trial. Part II: Assessment of Safety. Rational Pharmacotherapy in Cardiology. 2021;17(5):668-673. (In Russ.) https://doi.org/10.20996/1819-6446-2021-10-06

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