Calcium antagonists and atherosclerosis

Calcium channel blockers (CCBs) have several properties which may have beneficial effects on the development of atherosclerosis. These include inhibition of vascular smooth muscle cell (SMC) proliferation and migration; inhibition of calcium influx into the vascular wall; reduction of extracellular matrix synthesis; promotion of uptake and breakdown of low-density lipoproteins; protection of lipoproteins from oxidative modification; maintenance of endothelial cell function; inhibition of platelet activation; and reduction of blood pressure. Although some of these effects are only seen at high drug concentrations, the great majority of reports indicate that CCBs can attenuate atherogenesis in animal models, notably the cholesterol-fed rabbit. Several clinical trials have now attempted to determine the efficacy of these drugs in human atheromatous disease. The outcome of these studies, including the International Nifedipine Trial of Antiatherosclerotic Therapy (INTACT), the Montreal Nicardipine Trial, and the Multicenter Isradipine/Diuretic Atherosclerosis Study (MIDAS), are summarized in this review, in the context of trials currently in progress. The emerging evidence suggests that an antiatherosclerotic action can be demonstrated in patients but the extent and clinical importance of this effect have yet to be fully established.