Should calcium antagonists be used after myocardial infarction? Ischemia selectivity versus vascular selectivity.
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.
Opie
L H
LH
Ischaemic Heart Disease Research Unit of the Medical Research Council, Cape Town, South Africa.
D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D006333:Heart Failure / Q000517:prevention & control; D006801:Humans; D009203:Myocardial Infarction / Q000150:complications*; D014693:Ventricular Fibrillation / Q000517:prevention & control
D002121:Calcium Channel Blockers