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Neurocognitive effects associated with proprotein convertase subtilisin-kexin type 9 inhibitor use: a narrative review

Neurocognitive adverse events have been observed with the widespread use of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors or “statins,” which reduce low-density lipoprotein cholesterol (LDL-C) levels and subsequently cardiovascular risk. The United States Food and Drug Association directed man...

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Autores principales: Yuet, Wei C., Ebert, Didi, Jann, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944525/
https://www.ncbi.nlm.nih.gov/pubmed/33763200
http://dx.doi.org/10.1177/2042098620959271
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author Yuet, Wei C.
Ebert, Didi
Jann, Michael
author_facet Yuet, Wei C.
Ebert, Didi
Jann, Michael
author_sort Yuet, Wei C.
collection PubMed
description Neurocognitive adverse events have been observed with the widespread use of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors or “statins,” which reduce low-density lipoprotein cholesterol (LDL-C) levels and subsequently cardiovascular risk. The United States Food and Drug Association directed manufacturers of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors to monitor for neurocognitive adverse events due to their potent effects on LDL-C reduction, which is a proposed mechanism for neuronal cell dysfunction. Other proposed mechanisms for PCSK9 inhibitor-associated neurocognitive adverse events include N-methyl-d-aspartate receptor modulation, dysregulation of lipid and glucose metabolism, and patient-specific risk factors for cognitive impairment. The purpose of this narrative review article is to describe the proposed mechanisms, incidence of neurocognitive adverse events from phase II and III trials for PCSK9 inhibitors, neurocognitive assessments utilized in clinical trials, and clinical implications. Given the increasing prevalence of PCSK9 inhibitor use and the neurocognitive adverse events observed with prior lipid-lowering therapies, clinicians should be aware of the risks associated with PCSK9 inhibitors, especially when therapy is indicated for patients at high risk for cardiovascular events. Overall, the incidence of PCSK9 inhibitor-associated neurocognitive appears to be uncommon. However, additional prospective studies evaluating cognitive impairment may be beneficial to determine the long-term safety of these agents.
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spelling pubmed-79445252021-03-23 Neurocognitive effects associated with proprotein convertase subtilisin-kexin type 9 inhibitor use: a narrative review Yuet, Wei C. Ebert, Didi Jann, Michael Ther Adv Drug Saf Review Neurocognitive adverse events have been observed with the widespread use of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors or “statins,” which reduce low-density lipoprotein cholesterol (LDL-C) levels and subsequently cardiovascular risk. The United States Food and Drug Association directed manufacturers of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors to monitor for neurocognitive adverse events due to their potent effects on LDL-C reduction, which is a proposed mechanism for neuronal cell dysfunction. Other proposed mechanisms for PCSK9 inhibitor-associated neurocognitive adverse events include N-methyl-d-aspartate receptor modulation, dysregulation of lipid and glucose metabolism, and patient-specific risk factors for cognitive impairment. The purpose of this narrative review article is to describe the proposed mechanisms, incidence of neurocognitive adverse events from phase II and III trials for PCSK9 inhibitors, neurocognitive assessments utilized in clinical trials, and clinical implications. Given the increasing prevalence of PCSK9 inhibitor use and the neurocognitive adverse events observed with prior lipid-lowering therapies, clinicians should be aware of the risks associated with PCSK9 inhibitors, especially when therapy is indicated for patients at high risk for cardiovascular events. Overall, the incidence of PCSK9 inhibitor-associated neurocognitive appears to be uncommon. However, additional prospective studies evaluating cognitive impairment may be beneficial to determine the long-term safety of these agents. SAGE Publications 2021-03-08 /pmc/articles/PMC7944525/ /pubmed/33763200 http://dx.doi.org/10.1177/2042098620959271 Text en © The Author(s), 2021 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Review
Yuet, Wei C.
Ebert, Didi
Jann, Michael
Neurocognitive effects associated with proprotein convertase subtilisin-kexin type 9 inhibitor use: a narrative review
title Neurocognitive effects associated with proprotein convertase subtilisin-kexin type 9 inhibitor use: a narrative review
title_full Neurocognitive effects associated with proprotein convertase subtilisin-kexin type 9 inhibitor use: a narrative review
title_fullStr Neurocognitive effects associated with proprotein convertase subtilisin-kexin type 9 inhibitor use: a narrative review
title_full_unstemmed Neurocognitive effects associated with proprotein convertase subtilisin-kexin type 9 inhibitor use: a narrative review
title_short Neurocognitive effects associated with proprotein convertase subtilisin-kexin type 9 inhibitor use: a narrative review
title_sort neurocognitive effects associated with proprotein convertase subtilisin-kexin type 9 inhibitor use: a narrative review
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944525/
https://www.ncbi.nlm.nih.gov/pubmed/33763200
http://dx.doi.org/10.1177/2042098620959271
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