The PCSK9 revolution

Current status, controversies, and future directions

Bruce A. Warden, Sergio Fazio, Michael Shapiro

    Research output: Contribution to journalReview article

    1 Citation (Scopus)

    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.

    Original languageEnglish (US)
    JournalTrends in Cardiovascular Medicine
    DOIs
    StatePublished - Jan 1 2019

    Fingerprint

    LDL Cholesterol
    Cardiovascular Diseases
    Cholesterol
    Hyperlipoproteinemia Type II
    United States Food and Drug Administration
    Risk Reduction Behavior
    Homeostasis
    History
    Monoclonal Antibodies
    Proprotein Convertase 9
    Direction compound
    Therapeutics

    Keywords

    • Dyslipidemia
    • Lipid lowering therapy
    • Proprotein Convertase Subtilisin/Kexin Type 9 inhibitors

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

    Cite this

    The PCSK9 revolution : Current status, controversies, and future directions. / Warden, Bruce A.; Fazio, Sergio; Shapiro, Michael.

    In: Trends in Cardiovascular Medicine, 01.01.2019.

    Research output: Contribution to journalReview article

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    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.",
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