BEPRIDIL "TORSADE DE POINTES" INCIDENCES HAVE DECREASED IN FRANCE

BEPRIDIL "TORSADE DE POINTES" INCIDENCES HAVE DECREASED IN FRANCE, following issue of new package insert warnings that recommend a dose of 200 mg/day and caution about use of the drug in elderly patients, a clinical investigator from France told an American Heart Association annual symposium in Washington, D.C. on Nov. 13. A colleague, Jean Manouvrier, MD, Hopital Cardiologique, Lille, France, stated that bepridil is "an excellent anti-anginal drug which should be avoided in the elderly patient and used with precaution when associated with diuretics (monitor potassium levels) or any other drug susceptible of increasing QT intervals (quinidines, amiodarone) or of reducing cardiac rate." Johnson & Johnson suspended bepridil clinical trials in the U.S. and U.K. in August after patient deaths resulting from adverse reactions were reported in France, where the drug remains on the market. The company subsequently modified its arrhythmia studies to exclude patients with ischemic heart disease and/or premature ventricular contractioins and resumed the trials. Manouvrier predicted that bepridil "will probably be released in the U.S. in the near future." The French researcher said bepridil's role in the onset of "torsade de pointes," a form of ventricular tachycardia, is "nondebatable." However, he suggested there were specific factors involved in the French cases. Manouvrier said the nine patients he had seen who experienced torsade de pointes were elderly, with an average age of 74 years, mostly female, and receiving bepridil in dosages of 300 mg/day, usually in conjunction with a diuretic. In another presentation at the session on ischemic heart disease drug therapy, Richard Katz, MD, George Washington University, described the findings of a bepridil-nifedipine multicenter study of 53 patients. He stated that bepridil is comparable to nifedipine in lack of proarrhythmic effects. An abstract of the study, Katz, et al, concluded that "despite bepridil induced prolongation of thw QT interval, it, like nifedipine, has no adverse effect on ventricular ectopy profile in patients with baseline low frequency ectopy." Distinguishing bepridil from the three calcium channel blockers currently available in the U.S., John Parker, MD, Queen's University, Kingston, Canada, pointed to bepridil's long half-life, which permits one-time daily dosage, and its unique electrophysiologic profile. Parker reported the results of a double-blind cross-over study of 18 patients with chronic stable angina who received 160 mg long acting propranolol, 300 mg bepridil, or placebo for four weeks. According to an abstract of Parker's study, "resting heart rate and rate pressure product were reduced with long acting propranolol and bepridil" while "long acting propranolol reduced exercise heart rate, systolic blood pressure and rate pressure product compared to placebo and bepridil." In addition, "treadmill walking time was prolonged similarly by both long-acting propranol and bepridil throughout the 24-hour study period." Investigators concluded that "bepridil is an effective antianginal agent in a single daily dose of 300 mg." Researchers at the Cardiac Dept., Zuiderzienhuis, Rotterdam presented a study of 70 patients with acute myocardial infarction who received 3 mg/kg/5 min. bepridil I.V. followed by 8 mg/kg/24 hours for severe angina not responding to nitrates and opiates. In 27 patients bepridil was also combined with beta blockers. In an abstract of the study, X. Hanno Krauss, et al, reported that "bepridil caused complete remission of pain in 38 patients, had partial success in 21 patients and no effect in 11 patients, six needing intra-aortic balloon pump therapy." The investigators concluded that "bepridil exerted immediate anti-anginal effects in 59 of 70 patients with severe angina" and its "use in acute myocardial infarction seems relatively safe even in combination with beta blockers."