Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.


The PCSK9 adventure — humanizing extreme LDL lowering

PCSK9 inhibitors are the most potent LDL-cholesterol lowering drugs on the market. The latest cardiovascular outcome trials of these anti-PCSK9 monoclonal antibodies show positive results with fully-human antibodies, although with modest effect on major adverse cardiovascular events in patients who attain LDL-cholesterol target levels with statin therapy, whereas humanized antibodies are associated with the development of neutralizing antibodies.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout

Figure 1: Fully-human versus humanized therapeutic monoclonal antibodies.


  1. Abifadel, M. et al. Living the PCSK9 adventure: from the identification of a new gene in familial hypercholesterolemia towards a potential new class of anticholesterol drugs. Curr. Atheroscler. Rep. 16, 439 (2014).

    Article  Google Scholar 

  2. Cohen, J. C., Boerwinkle, E., Mosley, T. H. Jr & Hobbs, H. H. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N. Engl. J. Med. 354, 1264–1272 (2006).

    Article  CAS  Google Scholar 

  3. Shapiro, M. D., Fazio, S. & Tavori, H. Targeting PCSK9 for therapeutic gains. Curr. Atheroscler. Rep. 17, 499 (2015).

    Article  Google Scholar 

  4. Ridker, P. M. et al. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N. Engl. J. Med. (2017).

  5. Sabatine, M. S. et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N. Engl. J. Med. 372, 1500–1509 (2015).

    Article  CAS  Google Scholar 

  6. Robinson, J. G. et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N. Engl. J. Med. 372, 1489–1499 (2015).

    Article  CAS  Google Scholar 

  7. Ridker, P. M. et al. Lipid-reduction variability and antidrug-antibody formation with bococizumab. N. Engl. J. Med. (2017).

  8. Sabatine, M. S. et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N. Engl. J. Med. (2017).

  9. Cannon, C. P. et al. Ezetimibe added to statin therapy after acute coronary syndromes. N. Engl. J. Med. 372, 2387–2397 (2015).

    Article  CAS  Google Scholar 

  10. Ray, K. K. et al. Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol. N. Engl. J. Med. 376, 1430–1440 (2017).

    Article  CAS  Google Scholar 

Download references


M.D.S. and S.F. were supported partially by NIH grant R01HL132985. The authors gratefully acknowledge Ms Deanna Plubell for assistance with the figure.

Author information

Authors and Affiliations


Corresponding authors

Correspondence to Michael D. Shapiro or Sergio Fazio.

Ethics declarations

Competing interests

M.D.S. received compensation for advisory activities from Alexion, Amgen, Bracco, and GE Healthcare. S.F. received compensation for advisory activities from Aegerion, Amarin, Amgen, Kowa, Merck, and Sanofi.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Shapiro, M., Fazio, S. The PCSK9 adventure — humanizing extreme LDL lowering. Nat Rev Cardiol 14, 319–320 (2017).

Download citation

  • Published:

  • Issue Date:

  • DOI:


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing