Treatment of unstable angina with emphasis on calcium antagonists

From the literature which has appeared over the last decade a selection was made of the three major calcium antagonists: nifedipine, verapamil and diltiazem. In the clinical situation, the net hemodynamic and electrophysiological effect of these drugs is the result of complex interactions between their peripheral and their central effects. The degree of baroceptor stimulation and reflex mediated beta-adrenergic activity, which counteracts and influences the intrinsic negative dromotopic, chronotopic and inotropic effects of calcium antagonists, are related to the degree of peripheral dilation. Nifedipine is the most potent arterial vasodilator and is consequently associated with the most intense reflex adrenergenic activity. Although their effects on vascular and cardiac muscle are similar but not identical, there exist major differences in their antiarrhythmic properties. All act as an antiarrhythmic agent when ischemia or reperfusion cause the arrhythmias, while verapamil selectively blocks the A-V node conduction. All three discussed calcium antagonists are effective in treating patients with coronary spasm, variant angina and unstable angina. In our personal experience with 73 patients with unstable angina with prolonged severe pain at rest with transient ST-segments and T-wavechanges without elevated enzyme levels, 21 became asymptomatic within 8 hours of treatment with conventional therapy, which included nitrates and betablockers. Of 52 who remained refractory to such therapy, the addition of 10 mg of nifedipine orally every two hours to a maximum of 60 mg rendered 42 of the 52 asymptomatic within 8 hours. Arguments why we believe that the timely administration of nifedipine to these and similar patients will reduce or delay the incidence of arrhythmias and myocardial infarction are given on the basis of experimental data. Nifedipine greatly dilates coronary arteries, an effect which persists even after the drug's general hemodynamic effects disappear. It is shown that antagonists have anti-ischemic properties which are primarily related to the persistent reduction of the basic coronary vascular tone which increases oxygen supply whilst reduced myocardial contractility leads to decreased oxygen consumption. Furthermore, preservation of cellular integrity is achieved via protection against intracellular Ca2+ excess, as demonstrated by preserved intracellular high energy phosphate. A randomized multicenter trial in the Netherlands is now in progress to clarify the definitive role of beta blockade versus calcium antagonists therapy of their combination in this syndrome.