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Current Atherosclerosis Reports
Published in: Current Atherosclerosis Reports 3/2015

01-03-2015 | Nonstatin Drugs (EM deGoma, Section Editor)

PCSK9 Inhibition: Current Concepts and Lessons from Human Genetics

Authors: Fatima Rodriguez, Joshua W. Knowles

Published in: Current Atherosclerosis Reports | Issue 3/2015

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Abstract

Low-density lipoprotein cholesterol (LDL-C) plays a central role in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Statins are the cornerstone of therapy for the treatment of elevated LDL-C and for the primary and secondary prevention of ASCVD. However, some patients are intolerant of statins or are unable to achieve acceptable lipid levels on statin-based regimens alone. Proprotein convertase subtilisin/kexin type 9 (PCSK9) serves as an important regulator of hepatocyte LDL receptor expression and degradation, and recent genetic studies have highlighted the critical role of PCSK9 in human disease. Gain-of-function mutations in PCSK9 are associated with familial hypercholesterolemia, whereas loss-of-function mutations are protective against ASCVD. Therefore, PCSK9 inhibition offers a promising supplement or alternative to statin therapy in the reduction of LDL-C. Numerous phase II and III randomized control trials have demonstrated the tolerability of monoclonal antibodies against PCSK9 and their efficacy in lowering LDL-C by an additional 40–70 %. In this article, we review the growing role of PSCK9 inhibition in LDL-C reduction for diverse patient populations.
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Metadata
Title
PCSK9 Inhibition: Current Concepts and Lessons from Human Genetics
Authors
Fatima Rodriguez
Joshua W. Knowles
Publication date
01-03-2015
Publisher
Springer US
Published in
Current Atherosclerosis Reports / Issue 3/2015
Print ISSN: 1523-3804
Electronic ISSN: 1534-6242
DOI
https://doi.org/10.1007/s11883-015-0487-8

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