A quarter century of drug treatment of dyslipoproteinemia, with a focus on the new HMG-CoA reductase inhibitor fluvastatin.
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.