Calcium channel blockers and coronary atherosclerosis: From the rabbit to the real world

Many calcium channel blockers have been shown to retard the development of atherosclerosis in cholesterol-fed rabbits. The mechanisms that may contribute to this effect include stimulation of cholesteryl ester hydrolase activity in smooth muscle cells, amelioration of hypercholesterolemic-induced endothelial dysfunction, or inhibition of smooth muscle cell proliferation and migration. The effect of calcium channel blockers on the evolution of coronary atherosclerosis in humans has been assessed in three clinical trials. In the Montreal Heart Institute trial, nicardipine did not influence the overall rate of progression and regression; however, patients treated with nicardipine experienced significantly less progression of minimal lesions, defined as stenoses of less than or equal to 20% severity. In the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT), nifedipine had no effect on overall progression and regression but, by one method of analysis, reduced the rate of appearance of new coronary lesions. In a preliminary report, diltiazem prevented the development of coronary atherosclerosis in heart transplant recipients. These studies indicate that calcium channel blockers retard the development of early atherosclerosis not only in animal models but also in human coronary arteries. Other studies recently completed or now under way will help to clarify the clinical role of calcium channel blockers in antiatherosclerotic therapy.