The effects of ketanserin on ventricular ectopic activity in humans

Summary

Ketanserin is a serotonin S₂-receptor antagonist that lowers blood pressure and inhibits platelet aggregation. Ketanserin treatment is also associated with prolongation of the corrected QT interval. The recently reported Prevention of Atherosclerotic Complications with Ketanserin (PACK) trial confirmed this prolongation of QT and also revealed a significant excess of deaths in patients receiving ketanserin together with potassium-losing diuretics. The investigators suggested that this excess of deaths may have been attributable to exacerbation of hypokalemia-induced ventricular arrhythmias by the repolarization-prolonging effect of ketanserin. However, drugs that prolong the QT interval may affect ventricular ectopic activity beneficially, and our study was designed to evaluate the effects of ketanserin on ventricular ectopic activity. Twenty patients (18 male, 2 female) aged 42–73 years were studied, each having at least 15 ventricular ectopic beats/hour. The study design was a double-blind, cross-over comparison of ketanserin, 40 mg twice daily, and placebo, both given for 1 week. Ventricular ectopic activity was assessed by 48-hour Holter electrocardiogram (ECG) tapes at the end of each treatment period. Ketanserin treatment was associated with prolongation of repolarization, as reflected by the significant mean increases in both QT interval (+30 ms; p<0.001) and corrected QT interval (+20 ms; p<0.05). The mean overall degree of ventricular ectopic activity, as represented by a score based on the Lown classification, was significantly reduced (p<0.05). This was associated with a concordant improvement in the individual indices of ectopic activity. Our results show that ketanserin significantly suppressed ventricular ectopic activity in our normokalemic patients. It would seem that the implications of ketanserin treatment for cardiac rhythm depend on the electrolyte environment. The drug appears to be potentially beneficial at normal potassium concentrations, but may carry the possibility of precipitating ventricular arrhythmias in the face of hypokalemia.