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PCSK9 Inhibitors: Potential in Cardiovascular Therapeutics

  • New Therapies for Cardiovascular Disease (K Mahaffey, Section Editor)
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Abstract

Despite the efficacy of statin therapy, patients treated with these agents face substantial residual risk that is associated with achieved levels of LDL cholesterol (LDL-C). These observations suggest a potential benefit of additional strategies to promote further LDL-C reduction. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as an attractive target in this regard. Abrogation of PCSK9 function prevents PCSK9-mediated catabolism of LDL receptors, increases cell surface LDL receptor density, and promotes clearance of LDL and other atherogenic lipoproteins from the circulation. Thus far, the most advanced approaches to block PCSK9 action are monoclonal antibodies and anti-sense oligonucleotides. Among statin-treated patients, these agents may produce additional LDL-C lowering exceeding 50 %. In rare genetic experiments of nature, individuals with dominant negative or dual loss of function mutations of PCSK9 appear to have no adverse health effects resulting from lifelong, very low levels of LDL-C. In short-term trials, PCSK9 antibodies have been generally well-tolerated. However, evidence to support long-term safety and efficacy of PCSK9 therapy to reduce cardiovascular risk awaits the results of large cardiovascular outcome trials.

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Acknowledgments

The authors express their appreciation to Ms. Carol Hudson, Dr. Marc Israel, and Dr. Bill Sasiela of Regeneron Pharmaceuticals for providing the figure in this manuscript.

Disclosure

Conflicts of interest: R.Q. Do: none; R.A. Vogel: serves as a consultant to Sanofi; has a pending appointment as national coordinator on Phase III trial; G.G. Schwartz: Through his institution, has received research support from Sanofi, Roche, and Anthera .

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Authors and Affiliations

  1. VA Medical Center, Denver, CO, 80220, USA

    Rose Q. Do, Robert A. Vogel & Gregory G. Schwartz

  2. University of Colorado Denver, Denver, CO, 80045, USA

    Rose Q. Do, Robert A. Vogel & Gregory G. Schwartz

  3. Cardiology Section 111B, VA Medical Center, 1055 Clermont St., Denver, CO, 80220, USA

    Gregory G. Schwartz

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  1. Rose Q. Do
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Correspondence to Gregory G. Schwartz.

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This article is part of the Topical Collection on New Therapies for Cardiovascular Disease

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Do, R.Q., Vogel, R.A. & Schwartz, G.G. PCSK9 Inhibitors: Potential in Cardiovascular Therapeutics. Curr Cardiol Rep 15, 345 (2013). https://doi.org/10.1007/s11886-012-0345-z

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