Background: Optimal, long-term drug strategies for cardioversion of atrial fibrillation (AF) and maintenance of sinus rhythm (SR) have been controversial. Amiodarone is an old drug that is an effective class III antiarrhythmic for both converting and maintaining sinus rhythm in patients with atrial fibrillation, however, there have been few recent, blinded, randomized controlled studies comparing amiodarone to other pharmacological agents to determine if it is an effective first-line therapy.
Hypothesis: Amiodarone when used as a first-line therapy is an effective pharmacological strategy for converting atrial fibrillation or maintaining sinus rhythm in patients with AF.
Study Design: A systematic review of randomized controlled studies.
Methods: A thorough electronic search of multiple databases including EBSCO, Medline, OVID, and PUBMED were conducted in the English language using “amiodarone,” “atrial fibrillation,” and “randomized controlled studies” as MeSH headings. Inclusion criteria were randomized controlled studies that included patients in all age groups with recent-onset, paroxysmal, persistent or chronic AF who were treated with either intravenous or oral amiodarone compared to placebo or another antiarrhythmic medication. Exclusion criteria were studies older than ten years that were not randomized controlled studies, amiodarone used in conjunction with other therapies, and post-surgical cardiac patients with recent-onset atrial fibrillation. Methodological quality of each study was evaluated using the JADAD score. Studies with a score of >3 were considered to be of high quality and were included in the review.
Results: Eight studies met the inclusion criteria for this review. All but one study demonstrated amiodarone’s efficacy in converting or maintaining sinus rhythm. The study comparing dofetilide to amiodarone for the conversion of either recent-onset AF or atrial flutter (Af) at three hours, proved to be more effective than amiodarone, with 35% of dofetilide patients converting to SR compared to only 4% in the amiodarone group (p < 0.001). In the study that evaluated conversion of either AF or Af to SR after 48 hours with ibutilide or amiodarone, findings were similar to that of dofetilide, but when AF was the only rhythm evaluated, there was no statistical difference between amiodarone and ibutilide at converting AF (69% vs. 77%, p = ns). However, when rapid cardioversion was desired in patients with AF or Af, ibutilide was faster at converting patients to SR compared to amiodarone (53.4 +/- 25.8 min vs. 492 +/- 186 min, p =0.000). Two studies evaluating the efficacy of amiodarone versus sotalol in maintaining SR at one year demonstrated amiodarone’s superiority over sotalol (p=0.002; AFFRIM substudy) and (p < 0.001; SAFE-T study) respectively, but when patients with ischemic heart disease were analyzed separately in the SAFE-T study, amiodarone was equally as effective as sotalol 4 in this patient subgroup (p=0.053) Two studies comparing amiodarone to class I antiarrhythmics including propafenone (AFFRIM substudy), or to propafenone and sotalol combined (CTAF study), found that amiodarone was superior in maintaining SR after one year (p < 0.001) and (p < 0.001) respectively, while in Kochaidakis et al comparing amiodarone to propafenone alone found no statistically significant difference between them for the suppression of recurrent symptomatic AF (p = 0.44). This finding was true only when adverse events were factored into the primary endpoint. Without adverse events amiodarone was slightly more effective than propafenone, and was just shy of statistical significance (p = 0.058). Three studies compared amiodarone to placebo for either maintaining SR or cardioverting AF. One study found amiodarone was more effective than placebo in maintaining AF after one year (p < 0.001; SAFE-T study), and Vardas et al found amiodarone was more effective than placebo in converting patients to sinus rhythm at the 30-day mark (OR 6.21%; 95% CI, 3.33 to 11.57; p < 0.0001). In contrast, the third study comparing dofetilide to amiodarone or placebo found that amiodarone was no more effective than placebo after 3 hours for cardioverting AF, where 4% of patients in the amiodarone group compared to 4% of patients in the placebo group had cardioverted at three hours. The final study evaluating the efficacy of digoxin verses amiodarone or sotalol in converting recent-onset AF to SR, found digoxin was inferior to amiodarone and sotalol combined (p < 0.05; RR 5.4.; 95% CI 1.5 to 19.2), while sotalol versus amiodarone showed no statistical difference (p=0.23).
Conclusion: In all but one study, amiodarone proved to be an effective first-line medication for the conversion or maintenance of sinus rhythm in patients with atrial fibrillation. However, its use as a first-line agent in symptomatic recent-onset AF is less effective than either ibutilide or dofetilide when prompt time to conversion is required. Amiodarone also proved to be more effective than sotalol in maintaining SR after one year, and demonstrated superior effectiveness when compared to class I antiarrhythmics. When compared to propafenone, amiodarone demonstrated either equal or superior effectiveness for maintaining SR at one year. However, because propafenone is a class I-C antiarrhythmic, it is contraindicated in patients with underlying structural heart disease, whereby amiodarone is a reasonable first-line alternative.
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