New Strategies for Lowering Low-Density Lipoprotein Cholesterol for Cardiovascular Disease Prevention

Sean Paul Gaine, Renato Quispe, Jaideep Patel, Erin D. Michos

Research output: Contribution to journalReview articlepeer-review

Abstract

Purpose of Review: The primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) relies on optimizing cardiovascular health and appropriate pharmacotherapy, a mainstay of which is low-density lipoprotein cholesterol (LDL-C) lowering. Typically, statin therapy remains the first-line approach. Advances in technology and understanding of lipid metabolism have facilitated the development of several novel therapeutic targets and medications within the last decade. This review focuses on medications recently approved by the US Food and Drug Administration (FDA) for the reduction of LDL-C and ASCVD risk, as well as new therapies in the pipeline. Recent Findings: Novel lipid therapies aim to lower risk of ASCVD by targeting reduction of atherogenic compounds, such as LDL, lipoprotein(a) (Lp(a)), and triglyceride-rich lipoproteins. Evolocumab and alirocumab, monoclonal antibody proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors which lower LDL-C by approximately 60%, have emerged as important therapies for use in patients with ASCVD as well as familial hypercholesterolemia (FH). Bempedoic acid, an ATP citrate lyase inhibitor, is an oral medication recently approved that can lower LDL-C by approximately 18% alone and 38% when combined with ezetimibe. Inclisiran, a small-interfering RNA (siRNA) molecule which inhibits the translation of PCSK9, is the most recently FDA-approved LDL-C lowering medication, and can reduce LDL-C by approximately 50% with twice-yearly subcutaneous dosing. The cardiovascular outcome trials for bempedoic acid and inclisiran are still ongoing. Evinacumab, a monoclonal antibody which targets angiopoietin-like protein 3 (ANGPTL3), has been approved for use in patients with homozygous FH. SiRNAs and antisense oligonucleotides (ASO) facilitating selective inhibition of the production of targeted proteins including Lp(a) and ANGLPTL3 are active areas of clinical investigation. Summary: Recently, several novel LDL-C lowering medications have been approved. New therapeutic targets have been identified and present additional means of lowering LDL-C and other atherogenic compounds for patients who remain at high ASCVD risk.

Original languageEnglish (US)
Pages (from-to)69-78
Number of pages10
JournalCurrent Cardiovascular Risk Reports
Volume16
Issue number9
DOIs
StatePublished - Sep 2022

Keywords

  • Apolipoprotein B
  • Atherosclerotic cardiovascular disease
  • Lipids
  • Lipoprotein(a)
  • Low-density lipoprotein cholesterol
  • Prevention
  • Triglycerides

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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