Incidence and clinical relevance of QT prolongation caused by the new selective serotonin antagonist ketanserin. Multicenter Ketanserin Research Group.
Efficacy and safety of ketanserin was studied prospectively in a randomized and double-blind trial involving 221 patients treated for hypertension and/or coronary artery disease. Since ketanserin has been suggested to cause QTc prolongation, we investigated the incidence and severity of this effect, as well as its influence on the incidence of malignant ventricular arrhythmias during Holter monitoring. After a 1-week run-in-period, all patients were examined, measuring blood pressure, electrocardiogram (ECG) and 24-hour Holter ECG. Two thirds of the patients (n = 147) were then randomized to ketanserin, 1 week 20 mg b.i.d. followed by 3 weeks 40 mg b.i.d.; one third of the patients (n = 74) received placebo b.i.d. for 4 weeks. After 4 weeks of treatment, blood pressure, ECG and 24-hour Holter ECG were performed. In hypertensive patients, ketanserin resulted in a significant reduction of systolic (mean reduction: -17 +/- 2 mm Hg; p less than 0.0001) and diastolic blood pressure (-12 +/- 1 mm Hg; p less than 0.0001) as compared to baseline, and to the placebo group (p less than 0.005 for systolic and diastolic blood pressure). The QTc interval was prolonged with ketanserin (mean value: 400 to 418 ms; p less than 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 QTc prolongation greater than 30 ms (p less than 0.01). QTc was not prolonged to greater than 500 ms in any patient. During Holter monitoring 128/147 patients (ketanserin group) and 61/74 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, though ketanserin prolonged QTc in one third of the patients, the drug was not arrhythmogenic or antiarrhythmic.
Zehender
M
M
Internal Medicine III, Department of Cardiology, University of Freiburg, FRG.
Meinertz
T
T
Hohnloser
S
S
Geibel
A
A
Hartung
J
J
Seiler
K U
KU
Just
H
H
D000368:Aged; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D003327:Coronary Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007650:Ketanserin / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016276:Ventricular Function / Q000187:drug effects
D007650:Ketanserin