A RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF PROPAFENONE IN THE PROPHYLAXIS OF PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA AND PAROXYSMAL ATRIAL-FIBRILLATION

Background Few antiarrhythmic agents have been shown in randomized con trolled trials to be effective and well tolerated in the prophylaxis o f paroxysmal supraventricular tachycardia or paroxysmal atrial fibrill ation. Propafenone, a class IC antiarrhythmic agent with weak beta-adr enoceptor antagonist properties, has shown promise in preliminary clin ical studies. Methods and Results A double-blind, placebo-controlled t rial of the efficacy and tolerability of propafenone was undertaken in 100 patients with paroxysmal supraventricular tachycardia ([PSVT] n=5 2) or atrial fibrillation/flutter ([PAF] n=48) who had recorded two or more symptomatic arrhythmia recurrences by transtelephonic ECG monito ring during a 3-month drug-free observation period. Patients were rand omized into two consecutive crossover periods of propafenone (300 mg B ID) versus placebo followed by 300 mg TID propafenone Versus placebo. Analysis was based on the time to treatment failure, defined as the in terval from treatment onset to the occurrence of either EGG-documented arrhythmia or an intolerable adverse event. With a proportional-hazar ds model, we determined the relative risk (95% confidence interval) of treatment failure after the achievement of steady-state drug levels f or placebo compared with propafenone 300 mg BID to be 6.8 (2.2 to 21.2 , P<.001, n=45) for PSVT and 6.0 (1.8 to 20.0, P=.004, n=30) for PAF. Due to a greater incidence of adverse events on high-dose propafenone, the relative risks of receiving placebo rather than propafenone 300 T ID were only 2.2 (0.9 to 5.3, P=.1, n=34) for PSVT and 1.9 (0.7 to 4.7 , P=.2, n=25) for PAF. However, if adverse events were excluded in the high-dose comparison, relative risks for arrhythmia recurrence were 1 5.0 (2.0 to 113, P=.009) for PSVT and incalculable (no preferences for placebo, P=.0002) for PAF. One episode of wide-complex tachycardia wa s documented during propafenone therapy. Conclusions Propafenone is of value in the prophylaxis of both PSVT and PAF. A dose of 300 mg BID i s effective and well tolerated. A larger dose of 340 mg TID causes mor e adverse effects but may be more effective in those who can tolerate it.