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Update on lipid-lowering therapy and LDL-cholesterol targets

Nature Clinical Practice Cardiovascular Medicine volume 3, pages 424–436 (2006)Cite this article

Abstract

Serum cholesterol has long been recognized as an important risk factor for the development and progression of atherosclerotic vascular disease. For more than 30 years, improved outcomes with lipid lowering have been demonstrated. As a result of these data, the National Heart, Lung, and Blood Institute (NHLBI) convened the National Cholesterol Education Program—Adult Treatment Panel I (NCEP ATP I). This panel and similar ones around the world have served to set the standards for lipid lowering in clinical practice. Subsequent revisions of these standards (NCEP ATP II and III) have led to greater focus being placed on LDL, and targets for lowering LDL levels being based on patients' risk of subsequent coronary disease events. Since the publication of the NCEP ATP III guidelines, several large-scale clinical trials of cholesterol lowering have been conducted, the findings of which have the potential to impact on clinical practice standards. In this article we focus on current guidelines for lipid-lowering therapy, review the results and implications of important completed clinical trials, and consider the utility of additional targets for preventive therapy, such as C-reactive protein and HDL. We also consider the prospects for treatments in development and future goals.

Key Points

  • Serum cholesterol plays an important part in the development and progression of coronary artery disease

  • Lowering of lipid levels, particularly with statins, has resulted in improved cardiovascular outcomes

  • Cholesterol treatment guidelines have evolved to focus primarily on LDL and have identified targets based on the individual patient's risk

  • Findings from clinical trials suggest benefit from lowering lipid levels to lower than previous targets in primary prevention, secondary prevention and following acute coronary syndromes

  • Overall data suggest that the greatest relative benefit is seen with intensive lipid-lowering therapy targeting to achieve the greatest reductions in LDL and the lowest levels

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Figure 1: Algorithm for lipid management based on the Third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice.
Figure 2: Resultant LDL levels and clinical event rates across multiple clinical secondary prevention trials.

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Authors and Affiliations

  1. Cardiovascular Division, Department of Medicine, members of the TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

    Stephen D Wiviott & Christopher P Cannon

  2. Cardiovascular Division, The TIMI Study Group, Brigham and Women's Hospital, 75 Francis Street, Boston, 02115, MA, USA

    Stephen D Wiviott

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  1. Stephen D Wiviott
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Corresponding author

Correspondence to Stephen D Wiviott.

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Competing interests

Christopher P Cannon has the declared the following competing interests: research funding received from Merck, AstraZeneca, and Merck/Shering Plough; lecture fees for continuing medical education conferences received from AstraZeneca, Bristol-Myers Squibb, Merck, Millennium, Pfizer, Sanofi-Aventis, and Schering Plough; honoraria for preparation of education materials received from BGB New York, DIME, i3 Magnifi, and NCME; and he has acted as a consultant on scientific or advisory boards for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Merck/Schering Plough, Pfizer, Sanofi-Aventis, and Shering Plough.

Stephen D Wiviott has the declared the following competing interests: research funding received from Eli Lilly, Sankyo Pharma, Sanofi-Aventis, Pfizer, Merck, Sanofi-Synthelabo, AstraZeneca, CV Therapeutics, and Corvas; honoraria for preparation of education materials received from Pfizer, Merck, Eli Lilly, Exeter Group, Annenberg Center, Partners International (Partners Health Care), Medical Decision Point (ESLM), Apollo Lipids, TheHEART.org, and Medical Education Systems Group; he has acted as a consultant for Amgen and Transform Pharmaceuticals; and he has been a member of the speakers bureau for Pfizer and Amgen.

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Wiviott, S., Cannon, C. Update on lipid-lowering therapy and LDL-cholesterol targets. Nat Rev Cardiol 3, 424–436 (2006). https://doi.org/10.1038/ncpcardio0613

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