LIMITS OF LIPID-LOWERING THERAPY - THE BENEFITS OF AMLODIPINE AS AN ANTIATHEROSCLEROTIC AGENT

Treatment of atherosclerosis has mainly focused on decreasing low-dens ity lipoprotein cholesterol (LDL-C). However, recent coronary angiogra phic trials revealed that aggressive lowering of LDL-C below 100 mg/dl arrests atherosclerosis progression in only 50-60% of patients. Furth ermore, quantitative coronary angiography in these trials showed signi ficant regression only in advanced fibrous-fatty plaques (greater than or equal to 50% stenosis) and not in the younger, more cell-prolifera tive lesions (< 50% stenosis). It is clear that lipid-lowering therapy has limited efficacy and there is therefore a need for other drugs, e specially anti-proliferative agents, for secondary and primary prevent ion. To test this hypothesis, a new calcium antagonist, amlodipine, wa s studied for its anti-atherogenicity in non-human primates because of its known in vitro anti-cell proliferant, cell membrane stabilising a nd anti-oxidant properties. Amlodipine was found to normalise elevated plasma levels of oxidised LDL without reducing elevated total LDL-C l evels in monkeys fed an atherogenic diet which, however, significantly suppressed atherosclerosis progression. These data suggest that amlod ipine may be an excellent candidate, in combination with lipid-lowerin g drugs, for dual therapy of atherosclerotic vascular disease and may also be effective as monotherapy even when LDL-C is not lowered satisf actorily.