Clinical Evaluation of Adverse Effects During Bepridil Administration for Atrial Fibrillation and Flutter

Abstract

Background Bepridil hydrochloride (Bpd) has attracted attention as an effective drug for atrial fibrillation (AF) and atrial flutter (AFL). However, serious adverse effects, including torsade de pointes (Tdp), have been reported. Methods and Results Adverse effects of Bpd requiring discontinuation of treatment were evaluated. Bpd was administered to 459 patients (361 males, 63±12 years old) comprising 378 AF and 81 AFL cases. Mean left ventricular ejection fraction and atrial dimension (LAD) were 66±11% and 40±6 mm, respectively. Adverse effects were observed in 19 patients (4%) during an average follow-up of 20 months. There was marked QT prolongation greater than 0.55 s in 13 patients, bradycardia less than 40 beats/min in 6 patients, dizziness and general fatigue in 1 patient each. In 4 of 13 patients with QT prolongation, Tdp occurred. The major triggering factors of Tdp were hypokalemia and sudden decrease in heart rate. There were no differences in the clinical backgrounds of the patients with and without Tdp other than LAD and age, which were larger and older in the patients with Tdp. Conclusion Careful observation of serum potassium concentration and the ECG should always be done during Bpd administration, particularly in elderly patients. (Circ J 2006; 70: 662 -666)

Importance of Morphological Changes in T-U Waves During Bepridil Therapy as a Predictor of Ventricular Arrhythmic Event

“…25, 26 In the present study, we observed ventricular arrhythmic events with considerable incidence, ie, 6/113 patients, so prediction of these events should be an extremely important issue during bepridil therapy. However, this incidence does not directly indicate the prevalence of ventricular arrhythmic event during bepridil therapy because 1 patient with arrhythmic episode was transferred to our hospital due to the event.…”

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

“…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. Yasuda et al investigated the incidence of side effects in a total of 459 patients treated with bepridil 13) . QT prolongation was observed in 13 cases (2.8%) and 4 cases (0.9%) among them developed TdP.…”

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

“…Bepridil-induced TdP has been reported to be more prevalent in patients with structural heart disease and in the presence of hypokalemia or marked bradycardia, conditions known to reduce the repolarization reserve and increase the spatial heterogeneity of ventricular repolarization. [10][11][12]14,45,46 Under such pathologic conditions, bepridil would further enhance the heterogeneity of ventricular repolarization to a critical level for the induction of TdP. Unraveling the spatial and dynamic modification of the action potential properties by bepridil in human hearts under such pathological conditions will be a subject for further investigation.…”

“…[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). [2][3][4][5] Spatially inhomogeneous prolongation of ventricular action potential duration (APD) through an inhibition of IKr (with or without concomitant inhibition of IKs) can provide a substrate for functional reentry leading to TdP.…”