Sotalol Amiodarone Atrial Fibrillation Efficacy Trial - SAFE-T
The goal of the trial was to evaluate the safety and efficacy of amiodarone compared with sotalol for restoration and maintenance of sinus rhythm among patients with atrial fibrillation.
Patients Screened: 6,582
Patients Enrolled: 665
Mean Follow Up: 12 to 54 months
Mean Patient Age: Mean age 67.1 years
Electrocardiographically documented atrial fibrillation for ≥72 hours that was present at randomization, and were receiving anticoagulants
Atrial flutter or paroxysmal atrial fibrillation, New York Heart Association class III or IV heart failure, creatinine clearance <60 ml/min, intolerance of beta-blockers, or history of long-QT syndrome
Time to recurrence of atrial fibrillation beginning on day 28
Patients were randomized in a double-blind manner to either amiodarone (n=267), sotalol (n=261), or placebo (n=137). Amiodarone dosing was 800 mg daily for 14 days, 600 mg daily for the next 14 days, 300 mg daily for the first year, and 200 mg daily for the remainder of the trial. Sotalol dosing was 80 mg twice daily for seven days and 160 mg twice daily for the remainder of the trial.
Patients had follow-up visits every four weeks and underwent ECG recordings and rhythm monitoring. Patients were followed from 12 to 54 months.
The large majority of patients enrolled in the trial were men (98.9%), as the trial was conducted by the Veterans Affairs Cooperative Study. Baseline characteristics were well balanced between the three groups, including the duration of atrial fibrillation (≤1 year in 73.8% of the amiodarone group, 78.9% of the sotalol group, and 80.3% of the placebo group) and presence of symptomatic atrial fibrillation (62.5%, 62.8%, and 60.6%, respectively).
Spontaneous conversion between randomization and day 28 occurred in 27.1% of the amiodarone group, 24.2% of the sotalol group (p=0.45), and 0.8% of the placebo group (p<0.001 for each compared to placebo). The primary endpoint of time to first recurrence of atrial fibrillation was longer in the amiodarone group (median 487 days, 48% by one year) compared with either the sotalol group (median 74 days, 68% by one year, p=0.002) or placebo group (median six days, 87% by one year, p<0.001 for both amiodarone and sotalol comparisons).
Results were similar in all subgroups, with the exception of patients with ischemic heart disease, which showed no difference between amiodarone and sotalol. Change in quality of life scores from baseline to one year did not differ by treatment group, with the exception of decrease in mental health score in the amiodarone group.
Adverse event rates were similar between the three groups. Minor bleeding occurred more frequently in the amiodarone group (8.33 per 100 patient-years of follow-up) compared with the sotalol group (6.37 per 100 patient-years of follow-up) or the placebo group (6.71 per 100 patient-years of follow-up).
Among patients with atrial fibrillation, treatment with amiodarone was associated with a longer time to recurrence of atrial fibrillation compared with sotalol or placebo. Sotalol was associated with a longer time to recurrence of atrial fibrillation compared with placebo, but was a shorter time compared with amiodarone. Spontaneous cardioversion in the first 28 days were similar in the amiodarone and sotalol groups, both of which were higher than the placebo group.
Singh BN, Singh SN, Reda DJ, et al. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med 2005;352:1861-72.
Keywords: Myocardial Ischemia, Follow-Up Studies, Veterans, Quality of Life, Electric Countershock, Electrocardiography, Sotalol, Mental Health
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