Lipid Lowering Drugs in Atherosclerosis—the HMG-CoA Reductase Inhibitors

Abstract

Arteriosclerosis, particularly coronary heart disease, is the leading cause of morbidity and mortality in many areas of the world. Elevated cholesterol, particularly LDL-cholesterol, has been shown to be one of the major modifiable factors in reducing coronary events. Standard hypolipidemic therapies include resin, fibrates and niacin. This review emphasizes a significant new therapeutic class of hypolipidemic agents, namely the HMG-CoA reductase inhibitors. These are potent cholesterol lowering agents. Lovastatin is the first agent of this class to receive clinical approval in the U.S.A. Simvastatin, an analog of lovastatin, is also approved in several countries. Both these agents are administered as lactones and hydrolyzed to the open acid forms. Another HMG-CoA reductase inhibitor pravastatin has recently been filed for registration in several countries. A fourth compound (SRI-62-320) which is currently in clinical investigation is a totally synthetic structure. If long-term safety remains good and clinical efficacy as demonstrated by reduction of cardiovascular events is proven, the HMG-CoA reductase class of agents will be a significant advance in the treatment of cardiovascular disease.