Cardiac effects of calcium antagonists in systemic hypertension

The calcium antagonists are a class of heterogeneous drugs, with a wide spectrum of direct and indirect cardiac effects that vary a great deal from one drug to another and depend upon formulation and duration of action. Calcium antagonists act by decreasing total peripheral resistance to lower arterial pressure. As a consequence, reflex tachycardia, increased cardiac output, and increased plasma catecholamine and plasma renin activity are commonly seen, particularly with the initial dose and with short-acting dihydropyridines. The abrupt vasodilation can paradoxically elicit angina and even acute myocardial infarction. These hemodynamic and neuroendocrine changes are less pronounced with the long-acting formulations. Most calcium antagonists diminish automaticity of the sinus node, slow conduction in the atrioventricular node, and have little, if any, effect on the automaticity of the myocytes. The dihydropyridines generally have less effect on automaticity and cardiac conduction than nondihydropyridines. The negative inotropic effect is most profound with nondihydropyridines and is greatly reduced or absent with newer dihydropyridines, such as isradipine, felodipine, amlodipine, and nisoldipine. Long-acting calcium antagonists generally improve myocardial oxygenation by unloading the heart, increasing coronary blood flow, and reducing myocardial oxygen consumption. Thus, calcium antagonists have a variety of beneficial effects in patients with hypertensive heart disease: they reduce left ventricular hypertrophy and its sequelae, such as ventricular dysrhythmias, impaired filling and contractility, and myocardial ischemia. Ongoing studies should provide a more conclusive answer regarding the efficacy and safety of calcium antagonists.