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.
Yamashita
Takeshi
T
The Cardiovascular Institute, Tokyo 106-0032, Japan. yamt-tky@umin.ac.jp
Ogawa
Satoshi
S
Sato
Toshiaki
T
Aizawa
Yoshifusa
Y
Atarashi
Hirotsugu
H
Fujiki
Akira
A
Inoue
Hiroshi
H
Ito
Makoto
M
Katoh
Takao
T
Kobayashi
Youichi
Y
Koretsune
Yukihiro
Y
Kumagai
Koichiro
K
Niwano
Shinichi
S
Okazaki
Osamu
O
Okumura
Ken
K
Saku
Keijiro
K
Tanabe
Teruhisa
T
Origasa
Hideki
H
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