New and Emerging Therapies for Reduction of LDL-Cholesterol and Apolipoprotein B: JACC Focus Seminar 1/4

Nick S. Nurmohamed, Ann Marie Navar, John J.P. Kastelein

Research output: Contribution to journalReview articlepeer-review

Abstract

Adding to the foundation of statins, ezetimibe and proprotein convertase subtilisin–kexin type 9 inhibitors (PCSK9i), novel, emerging low-density lipoprotein cholesterol (LDL-C)–lowering therapies are under development for the prevention of cardiovascular disease. Inclisiran, a small interfering RNA molecule that inhibits PCSK9, only needs to be dosed twice a year and has the potential to help overcome current barriers to persistence and adherence to lipid-lowering therapies. Bempedoic acid, which lowers LDL-C upstream from statins, provides a novel alternative for patients with statin intolerance. Angiopoetin-like 3 protein (ANGPTL3) inhibitors have been shown to provide potent LDL-C lowering in patients with homozygous familial hypercholesterolemia without major adverse effects as seen with lomitapide and mipomersen, and may reduce the need for apheresis. Finally, CETP inhibitors may yet be effective with the development of obicetrapib. These novel agents provide the clinician the tools to effectively lower LDL-C across the entire range of LDL-C–induced elevation of cardiovascular risk, from primary prevention and secondary prevention to null-null homozygous familial hypercholesterolemia patients.

Original languageEnglish (US)
Pages (from-to)1564-1575
Number of pages12
JournalJournal of the American College of Cardiology
Volume77
Issue number12
DOIs
StatePublished - Mar 30 2021
Externally publishedYes

Keywords

  • ANGPTL3
  • CETP
  • CVD
  • bempedoic acid
  • inclisiran
  • lipid lowering

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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