Efficacy and Safety of the Additional Bepridil Treatment in Patients With Atrial Fibrillation Refractory to Class I Antiarrhythmic Drugs

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)

“…Actually, in the present study, the drug administration had to be discontinued due to QT prolongation in 4 out of 29 patients (14%) undergoing a 200 mg/day treatment. This discontinuation rate seems somewhat higher than that in previous studies, [20][21][22][23][24] and the difference might be attributed to the randomization and double-blindness of the present study.…”

“…[20][21][22][23][24] They used low doses of bepridil (100-200 mg/day) for minimizing arrhythmogenic side effects in patients with persistent AF, and found that even a low-dose bepridil was effective for the conversion of persistent AF to sinus rhythm (approximately 70%) in selected patients without causing arrhythmogenic effects. However, at the same time, several case reports also on the side effects of using low doses of bepridil: sick sinus syndrome with torsades de pointes or interstitial pneumonitis.…”

“…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. [20][21][22][23][24] Since then, some Japanese specialists in cardiac electrophysiology gradually began carefully using a low-dose bepridil for persistent AF. However, those previous studies were performed in selected patients in selected institutions, and also in an open-label fashion.…”

Class IV Antiarrhythmic Agents: New Compounds Using an Old Strategy

“…For instance, when 50-200 mg/day bepridil was added to a class I antiarrhythmic drug the frequency of symptomatic AF episodes was reduced to less than 10 % in 78 % of the patients and SR was restored within 3 months and maintained during the follow-up in 74 % of patients with persistent AF. During a mean follow-up period of 27±22 months, no potential complications occurred in any of the patients [383]. Again, combined therapy of bepridil (200 mg/day) and a class IC antiarrhythmic drug was more efficient for pharmacological cardioversion of refractory long-lasting persistent AF than bepridil alone [384].…”

Opposing Effects of Bepridil on Ventricular Repolarization in Humans Inhomogeneous Prolongation of the Action Potential Duration vs Flattening of Its Restitution Kinetics

“…[1][2][3][4][5][6][7][8][9] Despite its usefulness for the treatment of AF, there remains some concern about the drug-induced polymorphic ventricular tachycardia, known as torsades de pointes (TdP), in association with QT prolongation. [10][11][12][13] The QT prolongation is attributable to the blockade of several K + outward currents, including the rapidly and slowly activating delayed rectifier K + currents (IKr and IKs).…”