QT prolongation and torsades de pointes during emergency treatment with nifekalant for refractory ventricular tachyarrhythmias: Post-hoc analysis from a large-scale multicenter post-marketing survey in Japan

Abstract

Background: Nifekalant, a first-line drug for the treatment of ventricular tachycardia/ventricular fibrillation (VT/VF) in Japan, has been known to prolong the QT interval; however, the incidence of excess QT/QTc prolongation and subsequent torsades de pointes (TdP) has not yet been reported. Methods: The QT/QTc interval and occurrence of TdP during nifekalant therapy were evaluated in 1402 emergency patients with VT/VF. Results: Thirty-five cases (2.5%) of QT/QTc prolongation and 54 cases (3.9%) of TdP were reported. High nifekalant doses and long QTc intervals were associated with frequent TdP. The incidence of TdP was 1.4% for QTc intervals <0.43, 3.9% for those 0.44–0.49, 5.3% for those 0.50–0.55, 7.3% for those 0.56–0.61, 11.1% for those 0.62–0.67, and 12.5% for those ≥0.68. The odds ratio for TdP was elevated in women (2.48); in patients with any heart disease (4.68), New York Heart Association (NYHA) III or IV (1.81), Forrester subset 2 or worse (2.13), depressed cardiac function (1.86), or liver dysfunction (2.06); and in patients who were receiving concomitant drugs (2.67). In 42 patients (77.8%), TdP required treatment with direct current shock or a second drug. Conclusion: Nifekalant was effective for refractory VT/VF, although careful observation of the QT/QTc interval and possible occurrence of TdP is required, especially in high-risk patients.

Keywords

• Nifekalant
• Class III antiarrhythmic drug
• Life-threatening ventricular arrhythmia
• QT prolongation
• Torsades de pointes