Incidence and clinical relevance of QT prolongation caused by the new selective serotonin antagonist ketanserin

Abstract

Efficacy and safety of ketanserin were studied prospectively in a randomized, double-blind trial involving 221 patients treated for hypertension or coronary artery disease, or both. Since ketanserin has been suggested to cause QT c prolongation, the incidence and severity of this effect were investigated, as was the incidence of malignant ventricular arrhythmias during Holter monitoring. After a 1-week run-in period, all patients were examined: blood pressure was measured and electrocardiograms and 24-hour Holter electrocardiograms were obtained. Two thirds of the patients (n = 147) were then randomized to receive ketanserin for 1 week (20 mg twice daily) followed by 3 weeks of 40 mg twice daily; one third of the patients (n = 74) received placebo (twice daily) for 4 weeks. After 4 weeks of treatment, blood pressure, electrocardiograms and 24-hour Holter electrocardiograms were repeated. In hypertensive patients, ketanserin significantly reduced systolic (mean reduction 17 ± 2 mm Hg, p < 0.0001) and diastolic blood pressure (12 ± 1 mm Hg, p < 0.0001) compared to baseline, and to the placebo group (p < 0.005 for systolic and diastolic blood pressure). The QT c interval was prolonged with ketanserin (mean 400 to 418 ms, p < 0.01) but not with placebo (399 vs 402 ms). In the ketanserin group 30% of patients and in the placebo group 8% of patients had QT c prolongation >30 ms (p < 0.01). QT c was not prolonged to >500 ms in any patient. During Holter monitoring 128 of 147 patients (ketanserin group) and 61 of 74 patients (placebo group) had ventricular premature beats; in 42 (ketanserin group) and 13 patients (placebo group) ventricular pairs and tachycardia were documented. Incidence and severity of the ventricular arrhythmias after 4 weeks of treatment were not different between the ketanserin and placebo groups. No sustained ventricular tachycardia occurred in any patient after ketanserin treatment. Thus, although ketanserin prolonged QT c in one third of the patients, it was not arrhythmogenic or antiarrhythmic.