THE IMPACT OF RANOLAZINE IN ADDITION TO AMIODARONE INFUSION IN THE RESTORATION OF SINUS RHYTHM IN PATIENTS WITH PAROXYSMAL ATRIAL FIBRILLATION

The aim of this work was to evaluate the contribution of approved dosages of ranolazine (R) to the relief of AF paroxysms in patients receiving infusion therapy with amiodarone (A).
The present study includes 133 patients. (66±10 years, 42% of men). All included patients developed paroxysmal atrial fibrillation that lasted less than 48 hours before amiodarone infusion. All patients had no contraindications for pharmacological cardioversion. All patients received an intravenous bolus of amiodarone 5 mg/kg followed by a continuous infusion of 50 mg/h. Amiodarone infusion lasted up to 48 hours and stopped at the time of restoration of sinus rhythm. Immediately after the rhythm was restored, patients were switched to oral amiodarone at a dose of 200 mg/day.
The included patients were divided into 3 groups, the 1st group (group A, 44 patients) received only amiodarone according to the protocol, the 2nd group (group P500+A, 42 patients) received 500 mg of ranolazine orally at the time of administration of the amiodarone bolus and it continued to be taken orally every 12 hours at the same dose (500 mg), 3rd group (group P1000+A, 47 patients) received 1000 mg of ranolazine orally at the time of administration of the amiodarone bolus and it continued to be taken orally every 12 hours at the same dose (1000 mg). Patients were not randomized into groups, but subsequent analysis showed that the patients had no significant differences in their demographic and clinical characteristics. The ECG was monitored throughout the infusion, and the moment of rhythm recovery was necessarily recorded on the ECG. Three time lags were identified (the first 12 hours, i.e. before taking the 2nd dose of ranolazine, the first 24 hours, i.e. before taking the 3rd dose of ranolazine and 48 hours). 
During the first 12 hours in group A, rhythm recovery occurred in 36% of patients, in the P500+A group, rhythm recovery occurred in 64% of patients (p = ,0177 between A and P500+A according to the Chi-square test), in the P1000+A group the rhythm was restored in 72% of patients (p=,0012 between A and P1000+A according to the Chi-square test). During the first 24 hours, the restoration of sinus rhythm occurred in groups A, P500+A and P1000+A in 66%, 83% (p=,1087 between A and P500+A according to Chi-square test) and 87% (p=,0305 between A and P1000+A according to the Chi-square test), respectively. After 48 hours, rhythm recovery was noted in 77%, 93% (p=,0862 between A and P500+A by Chi-square), 98% (p=,0071 between A and P1000+A by Chi-square) in groups A, P500+A and P1000+A. During the infusion of A and taking P, no significant side effects were noted.
In this study, the addition of ranolazine to amiodarone was safe and well tolerated, and was more effective than amiodarone. The combination of the maximum allowed dose of ranolazine 1000 mg every 12 hours with amiodarone infusion already in the first 12 hours of use shows the maximum efficiency - 72% restoration of sinus rhythm, which reaches 98% by 48 hours, significantly exceeding amiodarone monotherapy at all-time intervals with comparable tolerability. The use of a lower dose of ranolazine 500 mg every 12 hours with amiodarone infusion is significantly superior to amiodarone monotherapy at the beginning - in the first 12 hours and at the end - by 48 hours and can be recommended in case of individual intolerance to the maximum combination of P+A.

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