A double-blind, placebo-controlled study of ketanserin in patients with Prinzmetal's angina. Evidence against a role for serotonin in the genesis of coronary vasospasm

This study was designed to test the hypothesis of a possible role of serotonin in the pathogenesis of myocardial ischemia in patients with pure vasospastic angina, since serotonin is known to cause contraction in isolated coronary arteries. This effect, as well as serotonin-induced platelet aggregation, is reversed by ketanserin, a specific S2-receptor blocker. Five male patients (49 to 68 years old) with more than six episodes/day of myocardial ischemia at rest as characterized by ST segment elevation on the electrocardiogram (ECG) were selected for the study after a 2 day run-in period of continuous ECG Holter monitoring in the absence of any therapy except that with sublingual nitrates. In a double-blind crossover protocol they received consecutive infusions of 6 hr each of ketanserin (2 mg/hr iv, preceded by a 10 mg bolus in three patients) and placebo in the following sequence: ketanserin-placebo-ketanserin-placebo in the first and placebo-ketanserin-placebo-ketanserin in the second 24 hr period. The efficacy of the infused drug was tested by exposing platelet-rich plasma, obtained from the study patients at a fixed morning time before and during ketanserin infusions, to a series of serotonin concentrations from 10 5 to 10 8M in a conventional aggregometer. A complete suppression of aggregation curves in the range of serotonin concentrations tested resulted during administration of ketanserin. The efficacy of the drug in preventing ischemic episodes was assessed by computing the ischemic episodes (recorded by Holter monitoring) and nitroglycerin consumption in each 6 hr ketanserin period and in the corresponding placebo period. A total of 171 ischemic episodes were recorded, 33 of which (19%) were symptomatic. Total numbers of ischemic episodes were 94 during ketanserin and 77 during placebo. No consistent differences in numbers of ischemic episodes and nitroglycerin consumption were observed in the comparison of the corresponding ketanserin and placebo 6 hr periods. Also, severity, as assessed both by nitroglycerin consumption and ST segment elevation, was not affected by the drug; one patient required nitrate infusion after the first day of the trial owing to a worsening of symptoms. On the basis of the results of this trial it appears unlikely that serotonin can play an important role in vasospastic angina.