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Benjamin J. Ansell, MD; Karol E. Watson, MD, PhD; Alan M. Fogelman, MD

JAMA. 1999;282:2051-2057.

Context  The Second Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II) was issued without the benefit of multiple recently published large clinical trials.

Objective  To analyze the panel's guidelines for treatment of high cholesterol levels in the context of currently available clinical trial results.

Data Sources  MEDLINE was searched for all English-language clinical trial data from 1993 through February 1999 relating to the effects of cholesterol treatment on cardiovascular clinical outcomes.

Study Selection  Studies that were selected for detailed review assessed the effects of cholesterol lowering on either coronary events, coronary mortality, stroke, and/or total mortality, preferably by randomized, double-blind, placebo-controlled design. Selection was by consensus of a general internist, a lipid clinic director, and a researcher in atherosclerotic plaque biology. A core of 37 of the 317 initially screened studies were selected and used as the primary means by which to assess the guidelines.

Data Extraction  By consensus of the group, only prespecified end points of trials were included, unless post hoc analysis addressed issues not studied elsewhere.

Data Synthesis  Recent clinical trial data mostly support the Adult Treatment Panel II guidelines for cholesterol management. While existing trials have validated the target low-density lipoprotein cholesterol (LDL-C) goals in the report, studies are lacking that address mortality benefit from reduction below these levels. Few lipid-lowering trials have treated patients with low high-density lipoprotein cholesterol and/or elevated triglyceride levels with LDL-C levels at or below treatment goals.

Conclusions  Lipid-lowering therapy generally should be more aggressively applied to patients with diabetes and/or at the time of coronary heart disease (CHD) diagnosis. The evidence for statin use in secondary CHD prevention in postmenopausal women outweighs current evidence for use of estrogen replacement in this setting. Further studies are needed to address the effects of lipid modification in primary prevention of CHD in populations other than middle-aged men and to study markers of lipid metabolism other than LDL-C.

Author Affiliations: Division of General Internal Medicine/Health Services Research (Dr Ansell) and the Division of Cardiology (Dr Watson), Department of Medicine (Dr Fogelman), University of California, Los Angeles, School of Medicine.

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