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J Am Coll Cardiol, 2000; 35:1-10
© 2000 by the American College of Cardiology Foundation
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REVIEW ARTICLE

The evolving role of statins in the management of atherosclerosis

Carl J. Vaughan, MD, MRCPIa, Antonio M. Gotto, Jr., MD, DPhil, FACCa and Craig T. Basson, MD, PhD, FACCa

a Division of Cardiology, Department of Medicine, Weill Medical College of Cornell University, The New York Presbyterian Hospital, Starr 4, 525 East 68th Street, New York, New York 10021.USA

Manuscript received February 23, 1999; revised manuscript received August 3, 1999, accepted October 5, 1999.

Reprint requests and correspondence: Dr. Craig T. Basson, Director, Molecular Cardiology, Cardiology Division, Department of Medicine, Weill Medical College of Cornell University, Starr 4, 525 East 68th Street, New York, New York 10021.
ctbasson{at}mail.med.cornell.edu

Significant advances in the management of cardiovascular disease have been made possible by the development of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors—"statins." Initial studies explored the impact of statin therapy on coronary artery disease (CAD) progression and regression. Although the angiographic changes were small, associated clinical responses appeared significant. Subsequent large prospective placebo-controlled clinical trials with statins demonstrated benefit in the secondary and primary prevention of CAD in subjects with elevated cholesterol levels. More recently, the efficacy of statins has been extended to the primary prevention of CAD in subjects with average cholesterol levels. Recent studies also suggest that statins have benefits beyond the coronary vascular bed and are capable of reducing ischemic stroke risk by approximately one-third in patients with evidence of vascular disease. In addition to lowering low-density lipoprotein (LDL) cholesterol, statin therapy appears to exhibit pleiotropic effects on many components of atherosclerosis including plaque thrombogenicity, cellular migration, endothelial function and thrombotic tendency. Growing clinical and experimental evidence indicates that the beneficial actions of statins occur rapidly and yield potentially clinically important anti- ischemic effects as early as one month after commencement of therapy. Future investigations are warranted to determine threshold LDL values in primary prevention studies, and to elucidate effects of statins other than LDL lowering. Finally, given the rapid and protean effects of statins on determinants of platelet reactivity, coagulation, and endothelial function, further research may establish a role for statin therapy in acute coronary syndromes.

Abbreviations and Acronyms
  AFCAPS/TexCAPS = Air Force/Texas Coronary Atherosclerosis Prevention Study
  CAD = coronary artery disease
  CARE = Cholesterol and Recurrent Events trial
  HDL = high-density lipoprotein cholesterol
  HMG CoA = 3-hydroxy-3-methylglutaryl coenzyme A
  LDL = low-density lipoprotein cholesterol
  LIPID = Long-term Intervention with Pravastatin in Ischemic Disease study
  MI = myocardial infarction
  NCEP = National Cholesterol Education Program
  4S = Scandinavian Simvastatin Survival Study
  WOSCOPS = West of Scotland Coronary Prevention Study




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