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Effects of bepridil and diltiazem on ventricular repolarization in angina pectoris

  • Christian Funck-Brentano
    Correspondence
    Address for reprints: Christian Funck-Brentano, MD, Unité de Pharmacologie Clinique, Hôpital Saint-Antoine, 184 rue du Faubourg St-Antoine, 75012 Paris, France.
    Affiliations
    From the Clinical Pharmacology Unit, Saint-Antoine University Hospital, Paris, France

    From the R. L. CERM Laboratories, Riom, France

    From the Organon Laboratories, Oss, the Netherlands

    From the Department of Cardiology, Antoine-Beclére University Hospital, Clamart, France
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  • Philippe Coudray
    Affiliations
    From the Clinical Pharmacology Unit, Saint-Antoine University Hospital, Paris, France

    From the R. L. CERM Laboratories, Riom, France

    From the Organon Laboratories, Oss, the Netherlands

    From the Department of Cardiology, Antoine-Beclére University Hospital, Clamart, France
    Search for articles by this author
  • Juan Planellas
    Affiliations
    From the Clinical Pharmacology Unit, Saint-Antoine University Hospital, Paris, France

    From the R. L. CERM Laboratories, Riom, France

    From the Organon Laboratories, Oss, the Netherlands

    From the Department of Cardiology, Antoine-Beclére University Hospital, Clamart, France
    Search for articles by this author
  • Gilbert Motté
    Affiliations
    From the Clinical Pharmacology Unit, Saint-Antoine University Hospital, Paris, France

    From the R. L. CERM Laboratories, Riom, France

    From the Organon Laboratories, Oss, the Netherlands

    From the Department of Cardiology, Antoine-Beclére University Hospital, Clamart, France
    Search for articles by this author
  • Patrice Jaillon
    Affiliations
    From the Clinical Pharmacology Unit, Saint-Antoine University Hospital, Paris, France

    From the R. L. CERM Laboratories, Riom, France

    From the Organon Laboratories, Oss, the Netherlands

    From the Department of Cardiology, Antoine-Beclére University Hospital, Clamart, France
    Search for articles by this author
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      Abstract

      To examine the time-course and potential predictors of prolongation of ventricular repolarization with the calcium antagonist bepridil, the effects of bepridil (300 to 500 mg/day; n = 45) and diltiazem (180 to 300 mg/day; n = 42) on QT and QTc interval duration were analyzed in a randomized doubleblind study in patients with angina pectoris. Electrocardiograms were recorded before and 14, 28, 70 and 112 days after treatment was begun. After 14 days, bepridil prolonged QT interval by 26 ± 35 ms (range, −60 to 120 ms) and QTc (Bazett's formula) by 17 ± 33 ms (range, −73 to 107 ms) compared to baseline (both p < 0.05). QT or QTc did not significantly increase thereafter. However, among the 30 patients who had <40 ms QTc prolongation at day 14 compared with baseline, 13 (43%) exceeded this limit on at least 1 of the following visits. Diltiazem did not significantly alter QT or QTc intervals. The absolute change in QTc interval from baseline observed after 14 days of bepridil therapy was inversely proportional to the baseline QTc interval (r = −0.68; n = 42; p < 0.001). The degree of bepridil-induced QTc prolongation on day 14 correlated with pretreatment RR interval (r = 0.36; n = 42; p < 0.02). In conclusion, chronic administration of bepridil but not of diltiazem prolongs ventricular repolarization in patients with angina pectoris. The overall effects of bepridil therapy on QT and QTc intervals can be assessed by an electrocardiogram recorded after 14 days of treatment but subsequent measurements may be required in individual patients. A short baseline QTc interval and a slow initial heart rate may be potentially useful predictors of a greater QTc prolongation with bepridil.
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