TY - JOUR
T1 - The PCSK9 revolution
T2 - Current status, controversies, and future directions: The PCSK9 revolution
AU - Warden, Bruce A.
AU - Fazio, Sergio
AU - Shapiro, Michael D.
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2020/4
Y1 - 2020/4
N2 - 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.
AB - 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.
KW - Dyslipidemia
KW - Lipid lowering therapy
KW - Proprotein Convertase Subtilisin/Kexin Type 9 inhibitors
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U2 - 10.1016/j.tcm.2019.05.007
DO - 10.1016/j.tcm.2019.05.007
M3 - Review article
C2 - 31151804
AN - SCOPUS:85066112695
SN - 1050-1738
VL - 30
SP - 179
EP - 185
JO - Trends in Cardiovascular Medicine
JF - Trends in Cardiovascular Medicine
IS - 3
ER -