Ranolazine enhances the efficacy of amiodarone for conversion of recent-onset atrial fibrillation.
OBJECTIVE
Amiodarone is used commonly for pharmacological cardioversion of atrial fibrillation (AF), but it is limited by moderate efficacy and delayed action. Ranolazine and amiodarone are markedly synergistic in suppressing experimental AF in vitro, yet the clinical efficacy of ranolazine combined with amiodarone for AF conversion has only undergone minimal investigation. This prospective, single-blinded, randomized study compared the safety and efficacy of ranolazine added to amiodarone vs. amiodarone alone for conversion of recent-onset AF.


RESULTS
We enroled 121 patients (64 ± 10 years, 45% male) with recent-onset (<48 h duration) AF who were eligible for pharmacological cardioversion. Patients received either 24 h amiodarone infusion (loading dose 5 mg/kg followed by maintenance dose of 50 mg/h; n = 60), or amiodarone infusion at the same dosage plus a single oral dose of ranolazine 1500 mg (n = 61). Patients in the amiodarone plus ranolazine group compared with the amiodarone-only group showed significantly higher conversion rates at 24 h (87 vs. 70%, respectively; P = 0.024) and at 12 h (52 vs. 32%; P = 0.021), and shorter time to conversion (10.2 ± 3.3 vs. 13.3 ± 4.1 h; P = 0.001). Subgroup analysis identified higher 24 h conversion in patients with left atrial (LA) diameter >46 mm who received the combination treatment vs. amiodarone alone (81 vs. 54%; P = 0.02), whereas the efficacy of the two interventions did not differ among patients with LA diameter ≤46 mm (P = 0.77). There was modest QT prolongation in both the groups, no serious adverse reactions, and no pro-arrhythmic events.


CONCLUSIONS
Addition of ranolazine to amiodarone was safe and well tolerated in this study, and it demonstrated efficacy superior to amiodarone alone for conversion of recent-onset AF. These findings may have clinical implications by offering a simple therapeutic manoeuvre to enhance amiodarone's effectiveness for conversion of AF.
Third Cardiology Department, Hippokrateion Hospital, Aristotle University Medical School, 49 Konstantinoupoleos Street, 546 42 Thessaloniki, Greece kckoskinas@gmail.com.
Konstantinos C
KC
Koskinas
Third Cardiology Department, Hippokrateion Hospital, Aristotle University Medical School, 49 Konstantinoupoleos Street, 546 42 Thessaloniki, Greece.
Nikolaos
N
Fragakis
Cardiology Department, Athens Euroclinic, 11521 Athens, Greece.
Demosthenes
D
Katritsis
Third Cardiology Department, Hippokrateion Hospital, Aristotle University Medical School, 49 Konstantinoupoleos Street, 546 42 Thessaloniki, Greece.
Vassileios
V
Skeberis
Third Cardiology Department, Hippokrateion Hospital, Aristotle University Medical School, 49 Konstantinoupoleos Street, 546 42 Thessaloniki, Greece.
Vassileios
V
Vassilikos
D000083:Acetanilides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000284:Administration, Oral; D000368:Aged; D000638:Amiodarone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006115:Greece; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D000069458:Ranolazine; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome
D000083:Acetanilides; D000889:Anti-Arrhythmia Agents; D010879:Piperazines; D000069458:Ranolazine; D000638:Amiodarone
Amiodarone; Atrial fibrillation; Cardioversion; Ranolazine