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(Circulation. 2004;110:886-892.)
© 2004 American Heart Association, Inc.

New Drugs and Technologies

Update on Statins: 2003

Carl J. Vaughan, MD; Antonio M. Gotto, Jr, MD, DPhil

From the Division of Cardiology, Department of Medicine, Weill Medical College of Cornell University, New York, NY.

Correspondence to A.M. Gotto, Jr, c/o Jesse Jou, Weill Medical College of Cornell University, 445 E 69th St, Olin Hall 205, New York, NY 10021. E-mail amg_editorial@mail.med.cornell.edu

Received March 31, 2004; revision received May 28, 2004; accepted June 3, 2004.

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The number of significant developments in the years since the first version of this review has made necessary an update about the evolving role of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, in the management and prevention of cardiovascular disease.¹ Two contrasting events have dominated the statin field in the last 3 years. First, the withdrawal of cerivastatin in 2001 reignited the issue of statin safety. Second, the efficacy and safety of statins in both the primary and secondary prevention of cardiovascular disease in diverse patient populations have helped shape the most recent set of guidelines from the National Cholesterol Education Program (NCEP).² The NCEP’s Third Adult Treatment Panel (ATP III) forms the basis for contemporary lipid management. However, very recent trials suggest that even lower LDL cholesterol (LDL-C) targets may be indicated in high-risk patients. Improved understanding of the metabolism, safety, and clinical effects of this class of drugs has placed the statins at the forefront of drug strategies to treat dyslipidemia.

Mechanism of Action, Comparative Pharmacology, and Safety of Statins

HMG-CoA reductase is the rate-limiting enzyme for cholesterol formation in the liver and other tissues. By inhibiting HMG-CoA reductase, statins reduce the hepatocyte cholesterol content, stimulate expression of LDL receptors, and ultimately enhance removal of LDL-C from the circulation. X-ray crystallographic studies have determined the structures of the catalytic portions of HMG-CoA reductase in complex with statins.³ These studies show that the HMG-like moiety of statins occupies the HMG binding site of the reductase enzyme, thus sterically inhibiting the substrate from binding. Additional structural differences among the . . . [Full Text of this Article]

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