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Emerging Pharmacotherapy to Reduce Elevated Lipoprotein(a) Plasma Levels

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Abstract

Lipoprotein(a) is a unique form of low-density lipoprotein. It is associated with a high incidence of premature atherosclerotic disease such as coronary artery disease, myocardial infarction, and stroke. Plasma levels of this lipoprotein and its activities are highly variable. This is because of a wide variability in the size of the apolipoprotein A moiety, which is determined by the number of repeats of cysteine-rich domains known as “kringles.” Although the exact mechanism of lipoprotein(a)-induced atherogenicity is unknown, the lipoprotein has been found in the arterial walls of atherosclerotic plaques. It has been implicated in the formation of foam cells and lipid deposition in these plaques. Pharmacologic management of elevated levels of lipoprotein(a) with statins, fibrates, or bile acid sequestrants is ineffective. The newer and emerging lipid-lowering agents, such as the second-generation antisense oligonucleotides, cholesteryl ester transfer protein inhibitors, and proprotein convertase subtilisin/kexin type 9 inhibitors offer the most effective pharmacologic therapy.

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Fig. 1

Modified from Nordestgaard et al. [8]

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Author information

Authors and Affiliations

  1. College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, Davie, FL, 33324, USA

    Nathaniel Eraikhuemen

  2. Memorial Regional Hospital-Department of Pharmacy, 3501 Johnson Street, Hollywood, FL, 32301, USA

    Dovena Lazaridis

  3. College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, Tallahassee, FL, USA

    Matthew T. Dutton

Authors
  1. Nathaniel Eraikhuemen
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  2. Dovena Lazaridis
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Corresponding author

Correspondence to Dovena Lazaridis.

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Funding

No sources of funding were used to conduct this study or prepare this manuscript.

Conflict of interest

Nathaniel Eraikhuemen, Dovena Lazaridis, and Matthew T. Dutton have no conflicts of interest that are directly relevant to the content of this article.

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Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Author Contributions

Conceptualization: [Nathaniel Eraikhuemen]. All authors [Nathaniel Eraikhuemen], [Dovena Lazaridis], and [Matthew T. Dutton] contributed to the the literature search, data analysis, and drafted the originaly work. Critical revisions of the work were performed by [Nathaniel Eraikhuemen] and [Dovena Lazaridis]. All authors performed approval of the final submitted version of the manuscript.

Glossary

Glossary

JUPITER:

Rosuvastatin 20 mg versus placebo in prevention of cardiovascular (CV) EventsMENDEL-1: monoclonal antibody against PCSK9 to reduce elevated low-density lipoprotein cholesterol (LDL-C) in adults currently not receiving drug therapy for easing lipid levels.

MENDEL-2:

Monoclonal antibody against PCSK9 to reduce elevated LDL-C in subjects currently not receiving drug therapy for easing lipid levels-2.

LAPLACE-TIMI 57:

Low-density lipoprotein cholesterol (LDL-C) assessment with PCSK9 monoclonaL Antibody Inhibition Combined With Statin thErapy (LAPLACE.

LAPLACE-2:

LDL-C assessment With PCSK9 monoclonal antibody inhibition combined with statin therapy-2.

RUTHERFORD-1:

Reduction of low-density lipoprotein cholesterol (LDL-C) with PCSK9 inhibition in heterozygous familial hypercholesterolemia disorder study.

RUTHERFORD-2:

Reduction of LDL-C with PCSK9 inhibition in heterozygous familial hypercholesterolemia disorder study-2.

GAUSS-1:

Goal Achievement after utilizing an anti-PCSK9 antibody in statin intolerant subjects.

GAUSS-2:

Goal achievement after utilizing an anti-PCSK9 antibody in statin intolerant subjects-2.

OSLER-1:

Open label study of long term evaluation against LDL-C trial.

FOURIER:

Further cardiovascular outcomes research with PCSK9 inhibition in subjects with elevated risk

ODYSSEY:

Evaluation of cardiovascular outcomes after an acute coronary syndrome during treatment with alirocumab

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Eraikhuemen, N., Lazaridis, D. & Dutton, M.T. Emerging Pharmacotherapy to Reduce Elevated Lipoprotein(a) Plasma Levels. Am J Cardiovasc Drugs 21, 255–265 (2021). https://doi.org/10.1007/s40256-020-00437-7

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