QT interval effects of Cisapride in the clinical setting

Abstract

Purpose: The clinical effect of cisapride on QT intervals was prospectively studied. Subjects: Consecutive adult patients were recruited in whom cisapride was indicated for gastroesophogeal reflux, gastric ulcer, duodenal ulcer, diabetic gastroparesis or chronic constipation refractory to laxatives. Exclusion criteria included disorders and medications affecting cardiac conduction, electrolyte homeostasis, drug clearance and membrane stability. Methods: Seventy-five patients were included and followed at 1 to 2 week intervals. Patients took cisapride 5 mg thrice daily for 1 to 4 weeks (lower dose stage), followed by 10 mg thrice daily for another 1 to 4 weeks (higher dose stage). Twelve-lead ECGs were performed before commencing cisapride (group B), at completion of the lower dose stage (group L) and at completion of the higher dose stage (group H). Results: No patients experienced presyncope or syncope. Seventeen patients failing to comply, and 7 complaining of abdominal discomfort or diarrhea were excluded, leaving 51 participants. Group H’s corrected QT interval (QTc) was longer than group B’s by 13±15 ms ( P<0.001), and longer than group L’s by 7±11 ms ( P<0.001). Group L’s QTc was longer than group B’s by 7±21 ms ( P<0.05). QT dispersion did not differ significantly among groups. Neither torsade de pointe nor ventricular tachycardia were noted in Holter monitoring of 33 patients during the higher dose stage. Conclusion: cisapride dose-dependently prolongs the QT interval. Further study is needed to examine the arrhythmogenicity of cisapride in higher doses and for longer durations.