Fluvastatin: effects beyond cholesterol lowering.
Coronary heart disease (CHD) remains a major therapeutic challenge in the Western world, and strategies aimed at cholesterol lowering form the mainstay of treatment. Fluvastatin is an established 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ("statin") for the treatment of hypercholesterolemia. Its efficacy and safety have been established in numerous clinical trials. Emerging evidence now indicates that treatment with fluvastatin slows the progression of atherosclerotic CHD and reduces the incidence of cardiovascular morbimortality in the secondary prevention setting. This effect of fluvastatin cannot be explained by cholesterol lowering alone; nonlipid-related mechanisms (so-called "pleiotropic effects") undoubtedly contribute to a certain extent, and are probably linked to modulation of the mevalonate pathway. This review discusses the experimental evidence regarding the antiatherosclerotic and antithrombotic effects of fluvastatin that may contribute to its beneficial action on disease progression and clinical events. Such effects include decreased expression of adhesion molecules in monocytes and leucocyte-endothelium adherence responses, immunomodulation, prevention of low-density lipoprotein oxidation, inhibition of cholesterol esterification and accumulation, along with effects on smooth muscle cell proliferation and migration. Pleiotropic actions aimed at plaque stabilization (eg, decreased secretion of matrix metalloproteinases by macrophages), together with effects on platelet activity, tissue factor expression, and endothelial function, may contribute to an antithrombotic effect of fluvastatin. Taken together, the results of these studies indicate that the effects of fluvastatin, at therapeutic doses, may extend beyond cholesterol lowering.
Corsini
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Institute of Pharmacological Sciences, University of Milan, Milan, Italy.
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000187:drug effects / Q000378:metabolism; D003327:Coronary Disease / Q000188:drug therapy / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology* / Q000627:therapeutic use; D000077340:Fluvastatin; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008798:Mevalonic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D000077340:Fluvastatin; D008798:Mevalonic Acid