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Targeting PCSK9 and Beyond for the Management of Low-Density Lipoprotein Cholesterol

Farzahna Mohamed1, Brett Mansfield1, Frederick J Raal1

  • 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa.

Journal of Clinical Medicine
|August 12, 2023
PubMed

Insights

New therapies beyond statins can significantly lower low-density lipoprotein cholesterol (LDL-C) and reduce atherosclerotic cardiovascular disease (ASCVD) risk. These innovative treatments offer alternatives for patients not reaching LDL-C goals or intolerant to statins.

Area of Science:

  • Cardiology
  • Pharmacology
  • Genetics

Background:

  • Elevated low-density lipoprotein cholesterol (LDL-C) is a primary driver of atherosclerotic cardiovascular disease (ASCVD).
  • Many patients, particularly those with familial hypercholesterolemia (FH) or very high ASCVD risk, fail to achieve target LDL-C levels with statin monotherapy.
  • Underutilization of novel lipid-lowering therapies (LLT) is attributed to cost and therapeutic inertia.

Purpose of the Study:

  • To review innovative approaches for managing elevated LDL-C beyond statin monotherapy.
  • To explore novel LLT strategies, including combination therapies and emerging targets.
  • To highlight advancements in nucleic acid-based therapies and gene editing for cardiovascular risk reduction.

Main Methods:

  • Review of current literature on novel lipid-lowering therapies.
  • Discussion of combination therapies involving statins with ezetimibe, bempedoic acid, and CETP inhibitors.
  • Exploration of targeted therapies like PCSK9 and ANGPTL3 inhibition, alongside nucleic acid-based and gene editing strategies.

Main Results:

  • Emerging LLT strategies demonstrate significant reductions in LDL-C.
  • These novel approaches offer improved cardiovascular outcomes.
  • New therapies provide viable alternatives for statin-intolerant patients and those with FH.

Conclusions:

  • Innovative LLT strategies, including combination therapies and targeted agents, are essential for optimal LDL-C control.
  • These approaches address the limitations of statin monotherapy and reduce ASCVD risk.
  • Advancements in nucleic acid-based therapies and gene editing promise enhanced patient adherence and improved cardiovascular health.

Keywords:
ANGPTL3 inhibitorsPCSK9 inhibitorsbempedoic aciddyslipidemia

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