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The PCSK9 revolution: Current status, controversies, and future directions.

Abstract
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) has revolutionized our understanding of cholesterol homeostasis and added to our arsenal against atherosclerotic cardiovascular disease (ASCVD). In a span of approximately 15 years, PCSK9 has morphed from an esoteric and rare cause of familial hypercholesterolemia (FH) into the most efficient cholesterol-lowering target ever known, with the completion of two large scale cardiovascular outcome trials showing positive results. Current Food and Drug Administration (FDA) approved modalities to inhibit PCSK9 are in the form of monoclonal antibodies which display an unparalleled degree of low-density lipoprotein cholesterol (LDL-C) lowering and expand upon the notion that lower LDL-C is better for ASCVD risk reduction. However, the accelerated pace of discovery and therapeutic development has left large gaps in our knowledge regarding the physiology and function of PCSK9. The aim of this review is to provide context to the discovery, history, treatment and current status of PCSK9 and its therapeutic inhibitors and highlight areas of controversy and future directions.
AuthorsBruce A Warden, Sergio Fazio, Michael D Shapiro
JournalTrends in cardiovascular medicine (Trends Cardiovasc Med) Vol. 30 Issue 3 Pg. 179-185 (04 2020) ISSN: 1873-2615 [Electronic] United States
PMID31151804 (Publication Type: Journal Article, Review)
CopyrightCopyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Anticholesteremic Agents
  • Biomarkers
  • Lipids
  • PCSK9 Inhibitors
  • Serine Proteinase Inhibitors
  • PCSK9 protein, human
  • Proprotein Convertase 9
Topics
  • Anticholesteremic Agents (adverse effects, therapeutic use)
  • Biomarkers (blood)
  • Cardiovascular Diseases (diagnosis, epidemiology, prevention & control)
  • Diffusion of Innovation
  • Dyslipidemias (blood, diagnosis, drug therapy, epidemiology)
  • Humans
  • Lipids (blood)
  • PCSK9 Inhibitors
  • Proprotein Convertase 9 (metabolism)
  • Risk Factors
  • Serine Proteinase Inhibitors (adverse effects, therapeutic use)
  • Time Factors
  • Treatment Outcome

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