The use of
calcium antagonists for postinfarct cardioprotection remains controversial. Several major trials have failed to show benefit, despite positive expectations based on promising experimental data. A clue to the problem with the
calcium antagonists was provided by the
diltiazem trial, in which an adverse effect in the presence of
congestive heart failure masked a benefit in those without
heart failure. Accordingly, the most recent trial, DAVIT-II, was carried out in patients in whom preexisting left ventricular failure had been excluded. One of the interesting byproducts of that study was the possibility that
verapamil prevented postinfarct
sudden death, which implies a potential antiarrhythmic mechanism. It is proposed that cytosolic
calcium overload could play a role in ischemic
ventricular fibrillation. Experimentally,
calcium antagonists are most effective
antifibrillatory agents when
catecholamine stimulation is combined with acute
ischemia, as would be the situation in the acute phase of
myocardial infarction. This potential benefit of
calcium antagonists may be offset in the presence of
congestive heart failure because left ventricular dilation is directly arrhythmogenic. The ideal
calcium antagonist, aimed at preventing postinfarct ischemic arrhythmias, but without a significant negative inotropic effect, could be based on 1 of 2 principles. First, the agent could be highly selective for the ischemic but not the nonischemic zone of the myocardium (ischemic-selective agent). Second, the agent could be highly vascular selective, so that left ventricular dilation would be avoided. A comparative study of these two types of
calcium antagonists should be undertaken in postinfarct patients.