3-Hydroxy-3-methylglutaryl--coenzyme A reductase inhibitors in the treatment of hypercholesterolemia.
A new class of drugs, which inhibit de novo cholesterol biosynthesis, significantly reduces the blood cholesterol concentrations in hypercholesterolemic patients. Four separate inhibitors have lowered plasma total cholesterol and low-density lipoprotein (LDL) levels in humans by 20% to 40%: mevastatin (Compactin), lovastatin (mevinolin), pravastatin (CS-514, Eptastatin, and SQ 31000), and simvastatin (Synvinolin, MK-733). In addition to lowering total and LDL cholesterol concentrations, the plasma concentration of the potentially atherogenic B apolipoprotein is also reduced by 20% to 40%. The reduction in the levels of circulating atherogenic lipoprotein particles occurs as a result of decreased synthesis and enhanced removal of LDLs by the LDL receptor pathway in hepatocytes. Moreover, the levels of high-density lipoprotein cholesterol, which are inversely related to atherosclerosis, increase in concentration with treatment by these drugs. If the short-term safety of these drugs extends to ongoing long-term studies and if cardiovascular morbidity and mortality are affected by their use, this class of hypolipidemic agent will markedly facilitate the effective treatment of hypercholesterolemia.
Hoeg
J M
JM
Molecular Disease Branch, National Heart, Lung, and Blood Institute, Bethesda, Md 20892.
Brewer
H B
HB
D000328:Adult; D000818:Animals; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D008078:Cholesterol, LDL / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008148:Lovastatin / Q000627:therapeutic use
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin