Disorders associated with the overproduction or delayed clearance of
beta-very low density lipoprotein and
low density lipoprotein (
LDL) are strikingly related to premature
coronary artery disease. There are five recognized classes of
LDL-lowering drugs, each acting through different basic mechanisms. The increased predictability, safety, and efficacy of newer
lipid-lowering agents have allowed controlled clinical trials to demonstrate conclusively that reducing
LDL leads to a reduction in
coronary artery disease.
Fluvastatin, a 3-hydroxy-3-methylglutaryl
coenzyme A (
HMG-CoA) reductase inhibitor, is almost completely absorbed, actively targeted to the liver, and secreted in the bile. It has no active circulating metabolites. The safety and efficacy of
fluvastatin have been demonstrated in more than 2,500 subjects treated in the United States, Canada, and Europe, and more than 1,000 have been treated for more than 1 year. Combination of
fluvastatin with
cholestyramine results in additional
cholesterol lowering. The
Lipoprotein and
Coronary Atherosclerosis Study, a randomized, double-blind trial of
fluvastatin using quantitative coronary angiography to measure
atherosclerotic plaque change and positron emission tomography to evaluate myocardial perfusion (myocardial flow reserve), illustrates the further exploration of
lipoproteins and
atherogenesis made possible by the availability of this new generation of
cholesterol-lowering agents.