A comparison of bepridil with amiodarone in the treatment of established atrial fibrillation.

Abstract

Fourteen patients with established atrial fibrillation (longer than three months) that was refractory to treatment were studied to compare the clinical and electrophysiological effects of amiodarone and bepridil. All patients initially received bepridil for three weeks (200-600 mg/day), followed by amiodarone for two to three months (100-400 mg/day). Bepridil seemed to be slightly more effective than amiodarone in converting the fibrillation to sinus rhythm (nine of fourteen compared with four of ten). The ventricular response in atrial fibrillation was equally well controlled by bepridil and amiodarone, both at rest and during exercise. Bepridil was associated with the development of ventricular arrhythmias in eight of fourteen patients; two had torsade de pointes, which in one degenerated into fatal ventricular fibrillation. These arrhythmias seemed to be associated with bepridil induced prolongation of the QTc interval. No ventricular arrhythmias were seen during amiodarone treatment. Although bepridil seems to be an effective antiarrhythmic agent for the management of atrial fibrillation, its arrhythmogenic actions make it unsuitable for this purpose.

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)

“…The first trial with the drug for AF was reported in comparison with amiodarone. 19 In this study, bepridil was used at a high dose of 400-600 mg/day for persistent AF, and the effects were compared to those produced by amiodarone, which was started at 800 mg/day and thereafter reduced to 200 mg/day. Nine of 14 patients were converted to sinus rhythm by the use of bepridil, while 4 of 10 were converted by amiodarone.…”

“…[12][13][14][15][16][17][18] In foreign countries, the antiarrhythmic effects of the drug were first examined based upon the experimental results in 1986. 19 Although bepridil at a high dose of 600 mg/day was effective for converting AF to sinus rhythm, it frequently caused remarkable QT prolongation and life-threatening arrhythmias including torsades de pointes. 19 The results estimated increased risks compared with the benefits, and therefore, the drug could not be used for AF treatment in the USA and Europe.…”

“…19 Although bepridil at a high dose of 600 mg/day was effective for converting AF to sinus rhythm, it frequently caused remarkable QT prolongation and life-threatening arrhythmias including torsades de pointes. 19 The results estimated increased risks compared with the benefits, and therefore, the drug could not be used for AF treatment in the USA and Europe. In the 2000's, several Japanese clinical studies reported that a low-dose bepridil (at 100-200 mg/day) was effective for converting persistent AF to sinus rhythm without causing any arrhythmogenic effects.…”

Drug-Induced Changes in Fibrillation Cycle Length and Organization Index Can Predict Chemical Cardioversion of Long-Lasting Atrial Fibrillation With Bepridil Alone or in Combination With Aprindine

“…In a previous study, bepridil (200-600 mg/day) was associated with the development of serious ventricular arrhythmias caused by excessive prolongation of the QT interval. 23 In the present study, however, the dosage of bepridil was 200 mg/day and serum K ≥3.8 mmol/L was maintained by administration of either an angiotensin-converting enzyme inhibitor or spironolactone to avoid the proarrhythmic effects of bepridil.…”

Current Strategy of Anti-arrhythmic Drug Therapy for Persistent Atrial Fibrillation

“…In Western countries, where the maximum dosage of bepridil (600 mg/day) used was significantly higher in clinical practice, TdP was frequently reported. Therefore, bepridil was branded as a drug with dangerous side effects and taken off the market despite its superior anti-arrhythmic actions 12) . Bepridil is still available in Japan at an appropriately lower dose (100-200 mg/day) and the evidence regarding efficacy and adverse effects, including TdP, has accumulated.…”