RYTHMOL SR has been evaluated in patients with a history of electrocardiographically documented recurrent episodes of symptomatic AF in 2 randomized, double-blind, placebo-controlled trials.

RAFT

In one U.S. multicenter trial (RAFT), 3 doses of RYTHMOL SR (225 mg twice daily, 325 mg twice daily, and 425 mg twice daily) and placebo were compared in 523 patients with symptomatic, episodic AF. The patient population in this trial was 59% male with a mean age of 63 years, 91% white, and 6% black. The patients had a median history of AF of 13 months and documented symptomatic AF within 12 months of trial entry. Over 90% were NYHA Class I, and 21% had a prior electrical cardioversion. At baseline, 24% were treated with calcium channel blockers, 37% with beta-blockers, and 38% with digoxin. Symptomatic arrhythmias after randomization were documented by transtelephonic electrocardiogram and centrally read and adjudicated by a blinded adverse event committee. RYTHMOL SR administered for up to 39 weeks was shown to prolong significantly the time to the first recurrence of symptomatic atrial arrhythmia, predominantly AF, from Day 1 of randomization (primary efficacy variable) compared with placebo, as shown in Table 3.

There was a dose response for RYTHMOL SR for the tachycardia-free period as shown in the proportional hazard analysis and the Kaplan-Meier curves presented in Figure 1.

Figure 1. RAFT Kaplan-Meier Analysis for the Tachycardia-Free Period from Day 1 of Randomization

In additional analyses, RYTHMOL SR (225 mg twice daily, 325 mg twice daily, and 425 mg twice daily) was also shown to prolong time to the first recurrence of symptomatic AF from Day 5 (steady-state pharmacokinetics were attained). The antiarrhythmic effect of RYTHMOL SR was not influenced by age, gender, history of cardioversion, duration of AF, frequency of AF, or use of medication that lowers heart rate. Similarly, the antiarrhythmic effect of RYTHMOL SR was not influenced by the individual use of calcium channel blockers, beta-blockers, or digoxin. Too few non-white patients were enrolled to assess the influence of race on effects of RYTHMOL SR.

No difference in the average heart rate during the first recurrence of symptomatic arrhythmia between RYTHMOL SR and placebo was observed.

ERAFT

In a European multicenter trial (European Rythmonorm SR Atrial Fibrillation Trial [ERAFT]), 2 doses of RYTHMOL SR (325 mg twice daily and 425 mg twice daily) and placebo were compared in 293 patients with documented electrocardiographic evidence of symptomatic paroxysmal AF. The patient population in this trial was 61% male, 100% white with a mean age of 61 years. Patients had a median duration of AF of 3.3 years, and 61% were taking medications that lowered heart rate. At baseline, 15% of the patients were treated with calcium channel blockers (verapamil and diltiazem), 42% with beta-blockers, and 8% with digoxin. During a qualifying period of up to 28 days, patients had to have 1 ECG-documented incident of symptomatic AF. The double-blind treatment phase consisted of a 4-day loading period followed by a 91-day efficacy period. Symptomatic arrhythmias were documented by electrocardiogram monitoring.

In ERAFT, RYTHMOL SR was shown to prolong the time to the first recurrence of symptomatic atrial arrhythmia from Day 5 of randomization (primary efficacy analysis). The proportional hazard analysis revealed that both doses of RYTHMOL SR were superior to placebo. The antiarrhythmic effect of propafenone SR was not influenced by age, gender, duration of AF, frequency of AF, or use of medication that lowers heart rate. It was also not influenced by the individual use of calcium channel blockers, beta-blockers, or digoxin. Too few non-white patients were enrolled to assess the influence of race on the effects of RYTHMOL SR. There was a slight increase in the incidence of centrally diagnosed asymptomatic AF or atrial flutter in each of the 2 treatment groups receiving RYTHMOL SR compared with placebo.