title: Anti-arrhythmic efficacy of nifekalant hydrochloride, a pure class III anti-arrhythmic agent, in patients with healed myocardial infarction and inducible sustained ventricular tachycardia.
abstract: In recent clinical trials, class III anti-arrhythmic drugs were found to reduce arrhythmic deaths in patients after myocardial infarction. The purpose of this study was to assess the electrophysiologic properties and anti-arrhythmic efficacy for inducible sustained ventricular tachycardias (VTs) of the pure class III agent nifekalant hydrochloride (MS-551) in comparison with those of procainamide. Programmed ventricular stimulation of up to three extra stimuli was performed for induction of VTs. Effective refractory period (ERP) of the ischemic zone and normal zone was also measured before and after nifekalant. Nifekalant and procainamide suppressed sustained VT induction in four of 15 patients and in six of 15 patients, respectively (p = NS). Sinus cycle length, PR interval, and QRS duration were not changed, but QT and QTc intervals were significantly increased with nifekalant (p < 0.01). Ventricular ERP also increased, whereas there were no significant differences in the increase of ERP between the ischemic and normal zones. The suppression of VT induction did not correlate with the changes in QT, QTc, and ERP after nifekalant administration. There were no significant differences in induced VT cycle length at baseline study between responders and nonresponders to nifekalant. Reverse use dependence was not apparent on review of electrophysiologic parameters. Neither proarrhythmic events nor hemodynamic disturbances occurred after nifekalant administration. It was concluded that nifekalant could be used safely and showed comparable effectiveness to procainamide for the suppression of VT induction.
authors.affiliation: Department of Cardiology, Yokosuka Kyosai Hospital, Kanagawa, and Department of Cardiovascular Medicine, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Igawa
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Aonuma
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Michiaki
authors.initials: M
authors.lastname: Hiroe
authors.forename: Masayasu
authors.initials: M
authors.lastname: Hiraoka
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
mesh_terms: D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D004562:Electrocardiography; D004594:Electrophysiology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000628:therapy; D011342:Procainamide / Q000627:therapeutic use*; D011744:Pyrimidinones / Q000627:therapeutic use*; D017180:Tachycardia, Ventricular / Q000517:prevention & control*
chemical_list: D000889:Anti-Arrhythmia Agents; D011744:Pyrimidinones; C076259:nifekalant; D011342:Procainamide