An interpretive history of the cholesterol controversy, part V: The discovery of the statins and the end of the controversy

Daniel Steinberg

Medicine, University of California San Diego, La Jolla, CA 92093-0682

Corresponding Author: dsteinberg{at}ucsd.edu

ABSTRACT The first four reviews in this series(1-4) 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 lowering blood cholesterol (using cholestyramine) significantly reduces coronary heart disease events. At that point, for the first time, lowering 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 up 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.

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