Evolution of calcium antagonists: past, present, and future.

Calcium antagonists were originally introduced as fast-acting vasodilators exhibiting powerful antihypertensive properties. They have now evolved into agents exhibiting a smooth onset and a long duration of action. Early agents, because of their rapid onset of action, were associated with a host of compensatory hemodynamic adverse effects including cardioacceleration and sympathetic stimulation. In contrast, the newer agents appear to retain the antihypertensive properties, but with an improved tolerability profile. Across the cardiovascular disease continuum, the presence of diabetes adds to the risk forcardiovascular events. In diabetic patients with hypertension, multiple drug therapy is clearly indicated. Agents such as calcium antagonists that normalize hemodynamics in this patient population might be expected to demonstrate beneficial effects on mortality. Evidence from the Systolic Hypertension in Europe and the Systolic Hypertension in China trials demonstrated over a 50% reduction in total mortality in the diabetic subgroup in patients treated with calcium antagonists. Among the calcium antagonists, particularly among the dihydropyridine subclasses, the efficacy of the drugs has been accompanied by some side effects, in particular pedal edema. The incidence of pedal edema is dose dependent and is the result of vasodilation and intracapillary hypertension. Newer calcium antagonists demonstrate antihypertensive efficacy similar to that of their predecessors but appear to have a reduced propensity to cause edema.