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Pharmacological strategies for lowering LDL cholesterol: statins and beyond

Nature Reviews Cardiology volume 8, pages 253–265 (2011)Cite this article

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Abstract

A continuous, graded relationship exists between LDL cholesterol (LDL-C) levels and risk of cardiovascular disease (CVD). This finding has been confirmed at progressively lower levels of LDL-C by results from clinical trials of therapies, particularly high-potency statins, which provide increasingly greater reductions in LDL-C levels. On the basis of this clinical trial evidence, progressively lower LDL-C goals for increasing numbers of patients, stratified by absolute CVD risk, have been recommended in guidelines for cholesterol management and CVD prevention. Some notable exceptions have been made, however, such as patients with end-stage renal disease or heart failure. To achieve low LDL-C goals, statins are first-line pharmacological therapy and can be combined with other agents to provide additional reductions in LDL-C levels as well as improvements in other lipoprotein fractions. Investigational agents that reduce LDL-C levels by other mechanisms are under development and could provide additional therapeutic strategies to achieve optimal LDL-C levels. These agents could be particularly appropriate for patients with severely elevated LDL-C levels, such as those with genetic dyslipidemia, for whom maximal drug therapy is insufficient to reduce LDL-C concentrations to recommended levels.

Key Points

  • Results from clinical trials have confirmed the persistence of the relationship between LDL cholesterol (LDL-C) and cardiovascular disease (CVD) at progressively lower levels of LDL-C

  • On the basis of available clinical trial evidence, guidelines for cholesterol management and CVD prevention have recommended progressively lower LDL-C goals

  • Statins are first-line drug therapy for reducing LDL-C levels in most patients

  • For patients in whom statin monotherapy does not reduce LDL-C concentrations to recommended levels, combination therapy with other lipid-regulating agents can further reduce the levels of LDL-C and other lipid fractions

  • Investigational agents that reduce LDL-C by different mechanisms than conventional therapy could provide additional strategies for reduction of LDL-C levels

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Figure 1: How antisense oligonucleotides block translation and thus inhibit protein production.
Figure 2: Assembly and secretion of VLDL and chylomicrons.
Figure 3: Mechanisms of PCSK9 action.

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  1. Department of Medicine, Section of Cardiovascular Research, Baylor College of Medicine, Methodist DeBakey Heart and Vascular Center, 6565 Fannin, M.S. A-601, Houston, 77030, TX, USA

    Ariel Brautbar & Christie M. Ballantyne

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C. M. Ballantyne and A. Brautbar researched data for the article, discussed the content, wrote the article, and reviewed/edited the manuscript before submission and after peer-review.

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C. M. Ballantyne has received grants/research support from Abbott, AHA, American Diabetes Association, AstraZeneca, GlaxoSmithKline, Merck & Co., NIH, Roche, Sanofi-Synthelabo, and Takeda. He has acted as a consultant for Abbott, Adnexus, Amylin, Bristol-Myers Squibb, Genentech, Idera Pharma, Kowa, Merck & Co., NicOx, Novartis, Resverlogix, Roche, Sanofi-Synthelabo, and Takeda. He has received speakers' bureau honoraria from Abbott, AstraZeneca, GlaxoSmithKline, and Merck & Co. A. Brautbar declares no competing interests.

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Brautbar, A., Ballantyne, C. Pharmacological strategies for lowering LDL cholesterol: statins and beyond. Nat Rev Cardiol 8, 253–265 (2011). https://doi.org/10.1038/nrcardio.2011.2

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