Verapamil following uncomplicated myocardial infarction: Promising, but not proven

There are no convincing data that any of the dihydropyridines reduce mortality, or major morbidity such as reinfarction, strokes, or hospitalization for congestive heart failure, and two recent studies suggest that the long-acting formulation of nifedipine and felodipine, another diHydropyridine, may also cause some sympathetic activation.

Abstract

n 1989, an overview of 28 randomized trials involving approximately 19,000 post-myocardial infarction patients concluded that calcium antagonists, when examined as a class, did not reduce mortality or reinfarction.’ In a subsequent overview following the publication of a few more trials over the next 2 years, it was apparent that there may be important differences in the effects of the subclasses of calcium antagonists and their impact on major vascular events. It appeared that the dihydropyridine calcium antagonists increased both mortality and reinfarction rates, whereas the nondihydropyridine calcium antagonists that did not increase heart rate, such as verapamil or diltiazem, did not appear to have an adverse effect.2 In particular, the trials with verapamil showed some promising results, with a trend toward a moderate reduction in reinfarction and no apparent excess in mortality (but with wide confidence intervals). In the last few months, several articles have rekindled interest in this topic. 3*4 Recent analysis of the old trials of nifedipine compared with plactbo in patients with ischemic heart disease has indicated an adverse dose response curve: Higher doses were associated with increased mortality. The preparation of nifedipine used in the trials was a short-acting preparation, which is associated with periodic decreases in blood pressure and significant neurohormonal activation. Therefore, it has been suggested that longer-acting preparations, which have a smoother action, may avoid this deleterious effect.5.” However, there are no clinical trial data to support this claim. Two recent studies suggest that the long-acting formulation of nifedipine and felodipine, another dihydropyridine, may also cause some sympathetic activation.‘,” Data with some of the newer dihydropyridines have raised concerns; one trial of isradipiney demonstrated a trend toward more cardiovascular events in hypertension patients, and another trial of fe1odipine’O reported more heart failure-related withdrawals. A recent, moderately large trial of amlodipine in heart failure suggested no clear overall evidence of benefit or harm.” Therefore, there are no convincing data that any of the dihydropyridines reduce mortality, or major morbidity such as reinfarction, strokes, or hospitalization for congestive heart failure. Although it is possible that some of the newer dihydropyridines or long-acting preparations may not be adverse and perhaps even beneficial, this can only be confirmed or refuted if prospective, large