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
Subscribe to Nature+
Get immediate online access to Nature and 55 other Nature journal
Subscribe to Journal
Get full journal access for 1 year
only $6.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
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).
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).
Shapiro, M. D., Fazio, S. & Tavori, H. Targeting PCSK9 for therapeutic gains. Curr. Atheroscler. Rep. 17, 499 (2015).
Ridker, P. M. et al. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N. Engl. J. Med. http://dx.doi.org/10.1056/NEJMoa1701488 (2017).
Sabatine, M. S. et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N. Engl. J. Med. 372, 1500–1509 (2015).
Robinson, J. G. et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N. Engl. J. Med. 372, 1489–1499 (2015).
Ridker, P. M. et al. Lipid-reduction variability and antidrug-antibody formation with bococizumab. N. Engl. J. Med. http://dx.doi.org/10.1056/NEJMoa1614062 (2017).
Sabatine, M. S. et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N. Engl. J. Med. http://dx.doi.org/10.1056/NEJMoa1615664 (2017).
Cannon, C. P. et al. Ezetimibe added to statin therapy after acute coronary syndromes. N. Engl. J. Med. 372, 2387–2397 (2015).
Ray, K. K. et al. Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol. N. Engl. J. Med. 376, 1430–1440 (2017).
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.
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.
About this article
Cite this article
Shapiro, M., Fazio, S. The PCSK9 adventure — humanizing extreme LDL lowering. Nat Rev Cardiol 14, 319–320 (2017). https://doi.org/10.1038/nrcardio.2017.66