Anti-atherosclerotic and vasculoprotective actions of calcium antagonists. Treatment of hypertension may prevent many of the complications attributable to blood pressure elevation, particularly those that are "pressure-related," such as stroke. However, the atherosclerotic complications of hypertension, e.g., coronary artery disease manifested as coronary morbidity and mortality, have not been reduced significantly with antihypertensive therapy. This disappointing outcome may reflect the adverse metabolic effects of the traditional therapies, diuretics and beta blockers, and their lack of specific vasoprotective properties. Increasing attention is thus being paid to the newer antihypertensive agents, which typically have fewer adverse effects and perhaps more physiologic mechanisms of antihypertensive action. Since calcium plays a key role in the genesis of atherosclerosis, calcium antagonists may positively affect the course of vascular disease. Investigators have observed that calcium antagonists display clear antiatherosclerotic properties in experimental as well as clinical studies. In one recently published clinical study, coronary artery disease was shown to develop more slowly, with a slower progression of individual stenoses, higher regression rate and less frequent occurrence of new lesions in patients treated chronically with verapamil compared to those receiving conventional therapies. Other similar investigations are currently under way to evaluate the antiatherogenic properties of calcium antagonists, including the Frankfurt Isoptin Progression Study (FIPS), the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS), the International Nifedipine Trial on Atherosclerosis Coronary Therapy (INTACT), and the large-scale Montreal Heart Institute Study. Results of these studies, which use precise end points such as myocardial infarction, cerebral infarction and peripheral vascular disease, may revolutionize the treatment of hypertension by identifying therapeutic approaches that control both the pressure-related and atherosclerotic complications of the disease. 