Clinical Outcome in Patients With Paroxysmal or Persistent Atrial Fibrillation Receiving Bepridil

Abstract

Background: It is unknown whether bepridil improves cardiovascular events in atrial fibrillation (AF) patients, so this study evaluated the clinical outcome in paroxysmal or persistent AF patients receiving bepridil. Methods and Results:We conducted a cohort study of 284 consecutive patients who received bepridil for AF (25% female, 59±13 years) with a median follow-up period of 17 months (4-157 months). A total of 135 (48%) patients had structural heart disease, and 231 patients (81%) had previously received class I or class III antiarrhythmic drugs. The cumulative rates for cardiovascular events were 2.4%, 8.1%, and 10.1% at 1, 3, and 5 years, respectively. The cumulative rates for a composite of mortality, cerebral infarction, systemic embolism, major bleeding and heart failure were 9.7%, 18.2%, and 29.6% at 1, 3, and 5 years, respectively. The probability of progression to permanent AF was 23.5% at 5 years. Sudden death occurred in a patient with a prior myocardial infarction who was taking 200 mg daily, and torsade de pointes (Tdp) occurred in two patients without structural heart disease taking 200 mg daily. Excessive corrected QT interval prolongation (>0.50 s) was observed when plasma concentrations were higher than 800 ng/ml. Conclusions:Bepridil might not improve the clinical outcome in refractory AF patients. Bepridil-related adverse events, including QT prolongation and Tdp, occurred in a dose- and concentration-dependent manner. (Circ J 2011; 75: 1334 - 1342

Guidelines for Therapeutic Drug Monitoring of Cardiovascular Drugs Clinical Use of Blood Drug Concentration Monitoring (JCS 2015) ― Digest Version ―

“…30- 34 The therapeutic range of bepridil is 250 to 800 ng/mL, and the risk of QT prolongation increases at plasma bepridil concentrations of >800 ng/mL. 33 The clearance of bepridil is low in low-body-weight individuals and elderly individuals. 35, 36 Monitoring blood bepridil concentrations is significant in order to assess the safety of treatment.…”

Guidelines for Pharmacotherapy of Atrial Fibrillation (JCS 2013)

“…125, 126 In Europe and the United States, the efficacy of amiodarone has been fully established, 127 and the drug is widely used to prevent AF recurrence in patients with different types of underlying disease and also in patients with intractable AF without structural heart disease. In Japan, the use of sotalol for this purpose is not covered by the NHI, and amiodarone as a drug to prevent AF is indicated only for patients with hypertrophic cardiomyopathy and those with heart failure.…”

The Relationship between the Plasma Concentration of Bepridil and Its Efficacy in the Treatment of Atrial Fibrillation in Japanese Patients

“…8) However, the sampling points and the length of treatment were not reported in that study. The biological half-life of bepridil is long (≥33 h), and we thought that it was necessary to define the sampling points and to allow several weeks after starting therapy to investigate the effect of dose on Cbep.…”