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Journal of Lipid Research, Vol. 47, 1339-1351, July 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Thematic Review

Thematic review series: The Pathogenesis of Atherosclerosis. An interpretive history of the cholesterol controversy, part V: The discovery of the statins and the end of the controversy¹

Daniel Steinberg²

Department of Medicine, University of California-San Diego, La Jolla, CA

¹ Based in part on the author's book in preparation, The Cholesterol Wars.

Published, JLR Papers in Press, April 3, 2006.

² To whom correspondence should be addressed. e-mail: dsteinberg{at}ucsd.edu

The first four reviews in this series (Steinberg, D. 2004. J. Lipid Res. 45: 1583–1593; Steinberg, D. 2005. J. Lipid Res. 46: 179–190; Steinberg, D. 2005. J. Lipid Res. 46: 2037–2051; Steinberg, D. 2006. J. Lipid Res. 47: 1–14) traced the gradual accumulation of evidence, evidence of several different kinds, supporting the lipid hypothesis. They tracked the history from Anitschkow's 1913 classic work on the cholesterol-fed rabbit model to the breakthrough 1984 Coronary Primary Prevention Trial, the first large, randomized, double-blind primary intervention trial showing that decreasing blood cholesterol (using cholestyramine) significantly reduces coronary heart disease events. At that point, for the first time, decreasing blood cholesterol levels became an official national public health goal. Still, only a small fraction of patients at high risk were getting appropriate cholesterol-lowering treatment, and a number of important clinical questions remained unanswered. This final review in the series traces the early studies that led to the discovery of the statins and briefly reviews the now familiar large-scale clinical trials demonstrating their safety and their remarkable effectiveness in reducing coronary heart disease morbidity and mortality.

Supplementary key words inhibition of cholesterol biosynthesis • triparanol • compactin • lovastatin

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