Suppression of paroxysmal atrial tachyarrhythmias--results of the SOPAT trial.

AIM: The indication to treat paroxysmal atrial fibrillation (PAF) is controversial. The Suppression of Paroxysmal Atrial Tachyarrhythmias (SOPAT) trial was designed to answer the following questions: (1) What is the average rate of spontaneous events of symptomatic PAF with and without anti-arrhythmic medication? (2) what is the prevalence of severe side-effects? and (3) is the fixed combination of Quinidine + Verapamil inferior to the efficacy of sotalol or not? METHODS AND
RESULTS: Within 60 months 172 centres in Germany, Poland, and The Slovak Republic prospectively enrolled 1033 patients (mean age 60 years, 62% male) with documented frequent episodes of symptomatic PAF. Patients were randomised to either Quinidine + Verapamil 480/240 mg/d (high dose; 263 patients), Quinidine + Verapamil 320/160 mg/d (low dose; 255 patients), Sotalol 320 mg/d (264 patients) or placebo (251 patients), of which 1012 patients entered the intention-to-treat analysis. The primary endpoint was the time to first recurrence of symptomatic PAF or premature discontinuation. Secondary outcome parameters were the total number of symptomatic episodes and tolerability of the tested drugs. Patients were followed for a period of up to 12 months by daily and symptom-triggered trans-telephonic ECG-monitoring (Tele-ECG). The mean time under treatment was 233 +/- 152 days. Regarding the primary endpoint, all active treatments were superior to placebo and not different from each other. A total of 756 patients reached the primary endpoint within 105.7 +/- 8.7 d (mean +/- SEM) in the placebo group, vs. Quinidine + Verapamil (high dose) (150.4 +/- 10 d, p = 0.0061), vs. Quinidine + Verapamil (low dose) (148.9 +/- 10.6 d, p = 0.0006), vs. Sotalol (145.6 +/- 93 d, p = 0.0007). All three treatments were also effective in the reduction of AF burden (days with symptomatic AF [%] mean +/- SD, p vs. placebo): Quinidine + Verapamil (high dose) (3.4 +/- 12, p = 0.0001), Quinidine + Verapamil (low dose) (4.5 +/- 12.3, p = 0.008) and Sotalol (2.9 +/- 6.5, p = 0.026) compared to placebo (6.1 +/- 13.5). A total of four deaths, 13 syncopes, and one ventricular tachycardia (VT) occurred during the active study period, of which one death and one VT were related to Quinidine/Verapamil.
CONCLUSION: Taken together, anti-arrhythmic therapy with the fixed combination of Quinidine + Verapamil is as effective as Sotalol in the reduction of the recurrence rate of symptomatic PAF with a low but definite risk of severe side-effects.

RCT Entities:   Population Interventions Outcomes