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

Bruce A. Warden, Sergio Fazio, Michael D. Shapiro

    Research output: Contribution to journalReview articlepeer-review

    61 Scopus citations


    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)
    Pages (from-to)179-185
    Number of pages7
    JournalTrends in Cardiovascular Medicine
    Issue number3
    StatePublished - Apr 2020


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

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine


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