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.


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 approximately 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.
The Cardiovascular Institute, Tokyo 106-0032, Japan. yamt-tky@umin.ac.jp
Takeshi
T
Yamashita
Satoshi
S
Ogawa
Toshiaki
T
Sato
Yoshifusa
Y
Aizawa
Hirotsugu
H
Atarashi
Akira
A
Fujiki
Hiroshi
H
Inoue
Makoto
M
Ito
Takao
T
Katoh
Youichi
Y
Kobayashi
Yukihiro
Y
Koretsune
Koichiro
K
Kumagai
Shinichi
S
Niwano
Osamu
O
Okazaki
Ken
K
Okumura
Keijiro
K
Saku
Teruhisa
T
Tanabe
Hideki
H
Origasa
D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D015764:Bepridil / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D023381:Endpoint Determination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods*; D011788:Quality of Life; D012008:Recurrence; D013685:Telecommunications / Q000295:instrumentation*; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D015764:Bepridil