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Beyond Statins and PCSK9 Inhibitors: Updates in Management of Familial and Refractory Hypercholesterolemias

  • Lipid Abnormalities and Cardiovascular Prevention (ED Michos, Section Editor)
  • Published:
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Abstract

Purpose of Review

Elevation in apolipoprotein B-containing lipoproteins in the blood is a cause of atherosclerosis. Statins have changed the preventive cardiology scenario, and more recently monoclonal proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors were added as robust agents to further reduce pro-atherogenic lipoproteins and therefore prevent cardiovascular events. However, despite this many dyslipidemic individuals persist with inadequate LDL-C levels and still at risk. The purpose of this review was to discuss current status and describe advances in therapies beyond statins and monoclonal PCSK9 inhibitors.

Recent Findings

Ezetimibe and lomitapide have been used for many years to further reduce LDL-C and longer term data reinforce their safety. Bempedoic acid, an inhibitor of adenosine triphosphate-citrate lyase, has been shown to add LDL-C reduction on top of statins and ezetimibe, furthermore it may be an alternative for statin intolerant patients. Inclisiran is a small interfering ribonucleic acid inhibitor that reduces the hepatic production of PCSK9 that induces robust LDL-C lowering, similar to monoclonal antibodies, with the advantage of 2 or 3 injections per year. So far, no safety signs were seen with its use. Evinacumab, a monoclonal antibody that binds angiopoietin-like protein 3 (ANGPTL3), induces robust LDL-C lowering in either homozygous familial hypercholesterolemia or severe hypercholesterolemia patients with good tolerability.

Summary

Many high-risk individuals persist with elevated LDL-C, newer medications further lower LDL-C on top of standard lipid-lowering therapies and are well tolerated. Ongoing clinical trials may prove if these novel medications will reduce cardiovascular events with safety.

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Funding

RDS is recipient of a scholarship from Conselho Nacional de Pesquisa e Desenvolvimento Tecnológico, Brazil (CNPq) No. 303734/2018-3.

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  1. Heart Institute-InCor, University of Sao Paulo Medical School Hospital, Av. Dr Enéas C. Aguiar 44, São Paulo, SP, 05403-900, Brazil

    Fabiana Rached & Raul D. Santos

  2. Hospital Israelita Albert Einstein, São Paulo, Brazil

    Raul D. Santos

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Rached, F., Santos, R.D. Beyond Statins and PCSK9 Inhibitors: Updates in Management of Familial and Refractory Hypercholesterolemias. Curr Cardiol Rep 23, 83 (2021). https://doi.org/10.1007/s11886-021-01514-2

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