Limits of lipid-lowering therapy: the benefits of amlodipine as an anti-atherosclerotic agent.
Treatment of atherosclerosis has mainly focused on decreasing low-density lipoprotein cholesterol (LDL-C). However, recent coronary angiographic trials revealed that aggressive lowering of LDL-C below 100 mg/dl arrests atherosclerosis progression in only 50-60% of patients. Furthermore, quantitative coronary angiography in these trials showed significant regression only in advanced fibrous-fatty plaques (> or = 50% stenosis) and not in the younger, more cell-proliferative lesions (< 50% stenosis). It is clear that lipid-lowering therapy has limited efficacy and there is therefore a need for other drugs, especially anti-proliferative agents, for secondary and primary prevention. To test this hypothesis, a new calcium antagonist, amlodipine, was studied for its anti-atherogenicity in non-human primates because of its known in vitro anti-cell proliferant, cell membrane stabilising and anti-oxidant properties. Amlodipine was found to normalise elevated plasma levels of oxidised LDL without reducing elevated total LDL-C levels in monkeys fed an atherogenic diet which, however, significantly suppressed atherosclerosis progression. These data suggest that amlodipine may be an excellent candidate, in combination with lipid-lowering drugs, for dual therapy of atherosclerotic vascular disease and may also be effective as monotherapy even when LDL-C is not lowered satisfactorily.
Kramsch
D M
DM
Division of Cardiology, University of Southern California Medical School, Los Angeles 90033, USA.
Sharma
R C
RC
D017311:Amlodipine / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000188:drug therapy*; D008078:Cholesterol, LDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood*
D000975:Antioxidants; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D017311:Amlodipine