Cardiovascular Journal of Africa: Vol 32 No 6 (NOVEMBER/DECEMBER 2021)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 32, No 6, November/December 2021 AFRICA 331 patients with amiodarone-induced hyperthyroidism for short- term discontinuation. 66 Regarding the combination of amiodarone with other anti-arrhythmics, it seems that the addition of ranolazine would produce conversion much faster than amiodarone in monotherapy. Tsanaxidis et al . studied a population of 173 patients, mean age of 68 years with recent-onset AF, enrolled for pharmacological cardioversion of AF. 67 The primary endpoint was the time to AF conversion in the amiodarone-versus- amiodarone + ranolazine group and the secondary endpoint was the conversion rate within 24 hours in the two groups. The authors demonstrated that the combination of amiodarone + ranolazine led to conversion to SR 10.8 hours faster than with amiodarone alone ( p < 0.0001). Furthermore, the 24-hour conversion rate with the combination of amiodarone + ranolazine was higher than with amiodarone in monotherapy (98 vs 58%, p < 0.001). Their results were confirmed by Koskinas et al ., who found in a group of 121 patients with recent-onset AF, a conversion time 3.1 hours shorter for the combination amiodarone + ranolazine compared to amiodarone in monotherapy ( p = 0.001), and a higher conversion rate of 81 vs 54% ( p = 0.02). 68 Efficacy of amiodarone in AF recurrence after direct-current conversion The success rate of electrical cardioversion was reported to be 75 to 87%, while the AF recurrence rate after conversion may be up to 50%, especially within four weeks. 69-71 Strong evidence supports that pre-treatment with amiodarone is effective in increasing not only the acute restoration of SR but also the long- term maintenance of SR. 72-74 The European Society of Cardiology (ESC) recommends anti-arrhythmic pre-treatment prior to conversion in order to enhance success and to prevent further AF recurrences. 1 If AAD is planned for SR maintenance after cardioversion, the guideline recommendation is to start amiodarone therapy a few weeks before cardioversion in order to achieve effective drug levels. However the guidelines assign this use of amiodarone to a class IIa recommendation with evidence level B (derived from a single randomised, controlled trial or large non-randomised studies). The most important studies on the use of amiodarone for the prevention of recurrent AF after conversion are listed in Table 4. Critical appraisal The literature search resulted in 1 035 publications on amiodarone use in adult patients with AF undergoing pharmacological or electrical cardioversion. Amiodarone was prescribed in the study group, while in the control group placebo or no treatment was used. Six studies including 528 patients were randomised, controlled trials and were published between 1995 and 2014. 52,57,73,75-77 Patients had persistent AF with a duration between one month and one year and received amiodarone 200 to 800 mg for one to 52 weeks. The left atrial diameter was 50 mm in all six studies and the length of follow up was one to 16 months. Overall, the long-term maintenance of SR was 34 to 50% for patients treated with amiodarone and five to 17% for patients treated with placebo or not receiving anti-arrhythmic drugs. The study of Channer et al . enrolled 161 patients with persistent AF, who were randomised to three groups: two groups of patients were treated before electrical conversion for two weeks with 400 mg amiodarone, and it was continued at a dose of 200 mg for eight weeks in one group and 52 weeks in the other, while the placebo group received placebo throughout the study. 73 Of the patients pre-treated with amiodarone, 21% (26/123) converted to SR before direct-current conversion (DCC), while Table 4. The most important randomised and non-randomised trials on the use of amiodarone for the prevention of AF recurrences after cardioversion Trial Amiodarone administration Number Mean age (years) Main results Galperin 2014 75 Amiodarone for maintenance of SR after cardioversion 51 68 81.5 vs 54.2% SR at 18 months Jong 2006 76 Amiodarone for maintenance of SR after cardioversion 76 66 38 vs 36% AF recurrence at 5 years between 200 and 100 mg amiodarone Vijayalakshmi 2006 52 Amiodarone in patients with AF with DCC 94 64 63 vs 16 in SR at 6 months between amiodarone and no drug Channer 2004 73 Amiodarone vs placebo before and after electrical cardio- version for persistent AF 161 67 51 vs 16% in SR at 8 weeks between amiodarone and placebo Boos 2004 77 Short-duration oral amiodarone after cardioversion of AF 35 61 47.1 vs 16.7% in SR at 16 months between amiodarone and placebo Manios 2003 57 Amiodarone and recurrence rate after cardioversion 111 64 26.4 vs 50% at 6 weeks between amiodarone and no drug GEFACA 2001 78 Amiodarone vs placebo for termination of persistent AF and maintenance of SR 95 63 79.54 vs 38.46% conversion to SR 37.14 vs 80% AF recurrence at 2.7 months CHF-STAT 1998 79 Amiodarone for maintenance of SR after in patients with AF + heart failure 103 67 31 vs 7.6% SR at 4 years amiodarone vs placebo Opolski 1997 80 Amiodarone for conversion and maintenance of SR after failed electrical cardioversion 49 62 65% SR after first ineffective DC cardioversion and followed by pre-treatment with amiodarone and repeat DCC 52% SR at 12 months Chun 1995 81 Amiodarone for maintenance of SR in patients with refractory AF 110 60 87% SR at 1 year 70% SR at 3 years 55% at 5 years Gosselink 1992 82 Amiodarone for maintenance of SR after cardioversion 89 63 53% SR at 3 years Brodsky 1987 83 Amiodarone for maintenance of SR after DCC in patients with dilated LA 28 61 39% SR at 6 months 35% SR at 1 year Gold 1986 84 Amiodarone for refractory AF 68 59 79% SR at 21 months Horowitz 85 Amiodarone for paroxysmal and persistent AF resistant to quinidine 38 60 55% in SR (of paroxysmal AF) and 45% SR (of persistent AF) at 15 months AF, atrial fibrillation; SR, sinus rhythm; DCC, direct-current conversion; LA, left atrium.