Treatment with Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i): Current Evidence for Expanding the Paradigm?
Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are low-density lipoprotein cholesterol (LDL-C)-lowering drugs that play a critical role in lipoprotein clearance and metabolism. PCSK9i are used in patients with familial hypercholesterolemia and for the secondary prevent...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2023-07-01
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| Series: | Journal of Cardiovascular Pharmacology and Therapeutics |
| Online Access: | https://doi.org/10.1177/10742484231186855 |
| _version_ | 1797780576241975296 |
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| author | Rosaria Vincenza Giglio BD, PhD Emir M. Muzurović MD, PhD Angelo Maria Patti MD, PhD Peter P. Toth MD, PhD Manyoo A. Agarwal MD Wael Almahmeed MD Aleksandra Klisic MD, PhD Marcello Ciaccio MD, PhD Manfredi Rizzo MD, PhD |
| author_facet | Rosaria Vincenza Giglio BD, PhD Emir M. Muzurović MD, PhD Angelo Maria Patti MD, PhD Peter P. Toth MD, PhD Manyoo A. Agarwal MD Wael Almahmeed MD Aleksandra Klisic MD, PhD Marcello Ciaccio MD, PhD Manfredi Rizzo MD, PhD |
| author_sort | Rosaria Vincenza Giglio BD, PhD |
| collection | DOAJ |
| description | Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are low-density lipoprotein cholesterol (LDL-C)-lowering drugs that play a critical role in lipoprotein clearance and metabolism. PCSK9i are used in patients with familial hypercholesterolemia and for the secondary prevention of acute cardiovascular events in patients with atherosclerotic cardiovascular disease (CVD). Methods: We focused on the literature from 2015, the year of approval of the PCSK9 monoclonal antibodies, to the present on the use of PCSK9i not only in the lipid field but also by evaluating their effects on metabolic factors. Results: PCSK9 inhibits cholesterol efflux from macrophages and contributes to the formation of macrophage foam cells. PCSK9 has the ability to bind to Toll-like receptors, thus mediating the inflammatory response and binding to scavenger receptor B/cluster of differentiation 36. PCSK9i lower the entire spectrum of apolipoprotein B-100 containing lipoproteins (LDL, very LDLs, intermediate-density lipoproteins, and lipoprotein[a]) in high CVD-risk patients. Moreover, PCSK9 inhibitors are neutral on risk for new-onset diabetes mellitus and might have a beneficial impact on the development of nonalcoholic fatty liver disease by improving lipid and inflammatory biomarker profiles, steatosis biomarkers such as the triglyceride-glucose index, and hepatic steatosis index, although there are no comprehensive studies with long-term follow-up studies. Conclusion: The discovery of PCSK9i has opened a new era in therapeutic management in patients with hypercholesterolemia and high cardiovascular risk. Increasingly, there has been mounting scientific and clinical evidence supporting the safety and tolerability of PCSK9i. |
| first_indexed | 2024-03-12T23:45:50Z |
| format | Article |
| id | doaj.art-faa1eeb0bb4341d0aad3475c053e45d6 |
| institution | Directory Open Access Journal |
| issn | 1940-4034 |
| language | English |
| last_indexed | 2024-03-12T23:45:50Z |
| publishDate | 2023-07-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Journal of Cardiovascular Pharmacology and Therapeutics |
| spelling | doaj.art-faa1eeb0bb4341d0aad3475c053e45d62023-07-14T07:33:39ZengSAGE PublishingJournal of Cardiovascular Pharmacology and Therapeutics1940-40342023-07-012810.1177/10742484231186855Treatment with Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i): Current Evidence for Expanding the Paradigm?Rosaria Vincenza Giglio BD, PhD0Emir M. Muzurović MD, PhD1Angelo Maria Patti MD, PhD2Peter P. Toth MD, PhD3Manyoo A. Agarwal MD4Wael Almahmeed MD5Aleksandra Klisic MD, PhD6Marcello Ciaccio MD, PhD7Manfredi Rizzo MD, PhD8 Department of Laboratory Medicine, University-Hospital, Palermo, Italy Department of Internal Medicine, Endocrinology Section, , Podgorica, Montenegro Internal Medicine Unit, “Vittorio Emanuele II” Hospital, Castelvetrano, Italy Ciccarone Center for the Prevention of Cardiovascular Disease, School of Medicine, Baltimore, MD, USA Heart and Vascular Thoracic Institute, , Abu Dhabi, UAE Heart and Vascular Thoracic Institute, , Abu Dhabi, UAE Primary Health Care Center, Podgorica, Montenegro Department of Laboratory Medicine, University-Hospital, Palermo, Italy Division of Endocrinology, Diabetes and Metabolism, University of South Carolina School of Medicine Columbia, Columbia, SC, USABackground: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are low-density lipoprotein cholesterol (LDL-C)-lowering drugs that play a critical role in lipoprotein clearance and metabolism. PCSK9i are used in patients with familial hypercholesterolemia and for the secondary prevention of acute cardiovascular events in patients with atherosclerotic cardiovascular disease (CVD). Methods: We focused on the literature from 2015, the year of approval of the PCSK9 monoclonal antibodies, to the present on the use of PCSK9i not only in the lipid field but also by evaluating their effects on metabolic factors. Results: PCSK9 inhibits cholesterol efflux from macrophages and contributes to the formation of macrophage foam cells. PCSK9 has the ability to bind to Toll-like receptors, thus mediating the inflammatory response and binding to scavenger receptor B/cluster of differentiation 36. PCSK9i lower the entire spectrum of apolipoprotein B-100 containing lipoproteins (LDL, very LDLs, intermediate-density lipoproteins, and lipoprotein[a]) in high CVD-risk patients. Moreover, PCSK9 inhibitors are neutral on risk for new-onset diabetes mellitus and might have a beneficial impact on the development of nonalcoholic fatty liver disease by improving lipid and inflammatory biomarker profiles, steatosis biomarkers such as the triglyceride-glucose index, and hepatic steatosis index, although there are no comprehensive studies with long-term follow-up studies. Conclusion: The discovery of PCSK9i has opened a new era in therapeutic management in patients with hypercholesterolemia and high cardiovascular risk. Increasingly, there has been mounting scientific and clinical evidence supporting the safety and tolerability of PCSK9i.https://doi.org/10.1177/10742484231186855 |
| spellingShingle | Rosaria Vincenza Giglio BD, PhD Emir M. Muzurović MD, PhD Angelo Maria Patti MD, PhD Peter P. Toth MD, PhD Manyoo A. Agarwal MD Wael Almahmeed MD Aleksandra Klisic MD, PhD Marcello Ciaccio MD, PhD Manfredi Rizzo MD, PhD Treatment with Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i): Current Evidence for Expanding the Paradigm? Journal of Cardiovascular Pharmacology and Therapeutics |
| title | Treatment with Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i): Current Evidence for Expanding the Paradigm? |
| title_full | Treatment with Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i): Current Evidence for Expanding the Paradigm? |
| title_fullStr | Treatment with Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i): Current Evidence for Expanding the Paradigm? |
| title_full_unstemmed | Treatment with Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i): Current Evidence for Expanding the Paradigm? |
| title_short | Treatment with Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i): Current Evidence for Expanding the Paradigm? |
| title_sort | treatment with proprotein convertase subtilisin kexin type 9 inhibitors pcsk9i current evidence for expanding the paradigm |
| url | https://doi.org/10.1177/10742484231186855 |
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