Treating hypercholesterolemia: looking forward.
Despite important advances in the management of hypercholesterolemia in recent decades, many patients with lipid disorders remain unidentified or undertreated and so continue to have unfavorable levels of low-density lipoprotein (LDL) cholesterol and an increased risk for coronary events. The statins--which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis--have proved to be the most powerful pharmacologic agents for lowering serum lipids, and newer statins offer even greater efficacy than the agents introduced 10 to 15 years ago. Studies have shown that rosuvastatin, in late-stage development, is a very potent agent for the treatment of primary hypercholesterolemia, and that relatively low doses decrease LDL cholesterol levels to a greater extent than do similar doses of pravastatin, simvastatin, or atorvastatin as evaluated in separate clinical trials. Pitavastatin, in phase II trials, also has promise as a more potent drug than currently available statins. Because neither of these drugs has been approved for use in the United States, clinical trial results should be considered preliminary. In the future, agents that combine the actions of statins and nicotinic acid may achieve still greater LDL cholesterol reductions. Drugs that lower lipids via mechanisms other than inhibition of HMG-CoA reductase also offer promise. The newest addition to the roster of lipid-regulating agents is ezetimibe, a cholesterol absorption inhibitor that has been approved for use either alone or in combination with a statin. Agents in development include bile acid transport inhibitors and inhibitors of acyl CoA:cholesterol acyltransferase. More research will be needed to determine the full clinical potential of such approaches to the management of hypercholesterolemia.
Gotto
Antonio M
AM
The Joan and Sanford I. Weill Medical College of Cornell University, New York, New York 10021, USA. pat2004@med.cornell.edu
D000924:Anticholesteremic Agents / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000187:drug effects* / Q000378:metabolism; D003324:Coronary Artery Disease / Q000209:etiology / Q000517:prevention & control*; D015507:Drugs, Investigational; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D008297:Male; D011379:Prognosis; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D015507:Drugs, Investigational; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors