Calcium antagonists during and after myocardial infarction

Calcium antagonists, or calcium channel entry blockers, have been advocated as cardioprotective agents in acute myocardial infarction (AMI) on the basis of animal experiments, which show that they will reduce the harmful effects of the calcium overload which follows ischaemia, particularly during reperfusion, and also that they will reduce coronary artery spasm. Unfortunately, these promising actions have not translated into clear mortality data. An overview of the large amount of data from properly randomised controlled clinical trials shows clear differences between the dihydropyridine class of calcium antagonists such as nifedipine, and the non-dihydropyridines verapamil and diltiazem. Most of the data with the former group derive from trials with short-acting formulations of nifedipine (TRENT, HINT, SPRINT-I and -II). Overall, none of these trials showed significant benefit in either AMI or post-MI prophylaxis. There was a trend for harm, with HINT stopped early because of excess reinfarction with nifedipine, compared with metoprolol. In contrast, and when taken together, the DAVIT-I and DAVIT-II studies with verapamil show significant reductions in sudden death, reinfarction and total mortality. The greatest benefit occurred in those patients with relatively good left ventricular function. Similar but less significant trends were seen in studies with diltiazem. It is clear that calcium antagonists, unlike beta-blockers, cannot be treated as a similar class. It seems likely that the adverse effects of nifedipine are related to reflex sympathetic cardiac stimulation as a result of the predominantly vasodilator action of these dihydropyridine compounds. Data on newer dihydropyridines with fewer reflex effects are awaited. In the meantime it seems sensible to use proven agents such as beta-blockers or verapamil. These data on AMI and the months following have recently been paralleled by case control studies in hypertension, which similarly have suggested harm from the use of predominantly short acting formulations of nifedipine compared with beta-blockers and which led to a warning statement by the US National Heart, Lung, and Blood Institute on 1 September 1995.