Dose-Response Effects of Bepridil in Patients With Persistent Atrial Fibrillation Monitored With Transtelephonic Electrocardiograms : A Multicenter, Randomized, Placebo-Controlled, Double-Blind Study (J-BAF Study)

Background: A multicenter, randomized, placebo-controlled, double-blind trial was conducted with patients with persistent atrial fibrillation (AF) to determine the dose-response effects and safety of bepridil, using every-day transtelephonic monitorings. Methods and Results: A total of 90 patients were randomized to receive placebo, 100 mg/day and 200 mg/day of bepridil treatment for 12 weeks. After the treatment, those patients who converted to sinus rhythm was 3.4% in placebo, 37.5% in those who received 100 mg/day and 69.0% in those who received 200 mg/day, thus demonstrating a linear dose-response relationship for AF conversion. The conversion rate gradually reached a maximal value at ~6 weeks after initiation of bepridil. However, the AF recurrence rate was high (91.7% in those receiving 100 mg/day and 75.0% in those receiving 200 mg/day). Adverse events, presumably related to the drug, were also frequent: ventricular tachycardia in 2, QT prolongation in 4 and sinus bradycardia in 2 patients. In those patients treated with 200 mg/day group, 1 patient died suddenly because of ventricular tachycardia. Conclusions: This study demonstrated the dose response-relationships of bepridil for AF conversion to sinus rhythm. However, the high rate of AF recurrence and substantial drug-related adverse effects, including sudden death, raised caution about using bepridil to treat persistent AF. The balance between benefits and risks of the drug should be individualized. (Circ J 2009; 73: 1020-1027)