Endocrinology and Metabolism

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Obesity and Metabolism
Role of PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia: Brian Tomlinson, Nivritti Gajanan Patil, Manson Fok, Christopher Wai Kei Lam; Endocrinol Metab. 2021;36(2):279-295. Published online April 19, 2021; DOI: https://doi.org/10.3803/EnM.2021.964

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Patients with familial hypercholesterolemia (FH) are at high or very high risk for cardiovascular disease. Those with heterozygous FH (HeFH) often do not reach low-density lipoprotein cholesterol (LDL-C) targets with statin and ezetimibe therapy, and those with homozygous FH (HoFH) usually require additional lipid-modifying therapies. Drugs that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) offer a novel approach to reduce LDL-C. The monoclonal antibodies, alirocumab and evolocumab, given by subcutaneous injection every 2 or 4 weeks produce reductions in LDL-C of 50% to 60% in patients with HeFH, allowing many of them to achieve their LDL-C goals. Patients with HoFH show a reduced and more variable LDL-C response, which appears to depend on residual LDL receptor activity, and those with receptor-negative mutations may show no response. Inclisiran is a long-acting small interfering RNA therapeutic agent that inhibits the synthesis of PCSK9. Subcutaneous doses of 300 mg can reduce LDL-C by more than 50% for at least 6 months and the responses in HeFH and HoFH patients are similar to those achieved with monoclonal antibodies. These PCSK9 inhibitors are generally well tolerated and they provide a new opportunity for effective treatment for the majority of patients with FH.

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Citations to this article as recorded by

Phenotypic homozygous familial hypercholesterolemia successfully treated with proprotein convertase subtilisin/kexin type 9 inhibitors
Ryosuke Tani, Keiji Matsunaga, Yuta Toda, Tomoko Inoue, Hai Ying Fu, Tetsuo Minamino
Clinical Case Reports.2024;[Epub] CrossRef
Targeting Lipoprotein(a): Can RNA Therapeutics Provide the Next Step in the Prevention of Cardiovascular Disease?
Henriette Thau, Sebastian Neuber, Maximilian Y. Emmert, Timo Z. Nazari-Shafti
Cardiology and Therapy.2024; 13(1): 39. CrossRef
Technologies of gene editing and related clinical trials for the treatment of genetic and acquired diseases: a systematic review
Wessam Sharaf-Eldin
Egyptian Journal of Medical Human Genetics.2024;[Epub] CrossRef
Qualitative and Quantitative Effects of PCSK9 Inhibitors in familial Hypercholesterolemia: a Synthetic Review
Aamina Shakir, Kyle Barron, Kalgi Modi
Current Problems in Cardiology.2023; 48(4): 101550. CrossRef
Inhibition of PCSK9 Improves the Development of Pulmonary Arterial Hypertension Via Down-Regulating Notch3 Expression
Peng Ye, Xiao-Min Jiang, Wei-Chun Qian, Juan Zhang
Cardiovascular Drugs and Therapy.2023;[Epub] CrossRef
Barriers and shortcomings in access to cardiovascular management and prevention for familial hypercholesterolemia during the COVID‐19 pandemic
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Clinical Cardiology.2023; 46(8): 831. CrossRef
Familial Hypercholesterolemia in Children. The Current State of the Problem
Dinara I. Sadykova, Karina R. Salakhova, Liliya F. Galimova, Eugeniya S. Slastnikova, Chulpan D. Khaliullina
Current Pediatrics.2023; 22(3): 231. CrossRef
Long-term safety and effectiveness of alirocumab and evolocumab in familial hypercholesterolemia (FH) in Belgium
Marc Snel, Olivier S. Descamps
Acta Cardiologica.2023; : 1. CrossRef
PCSK9 inhibitors revisited: Effectiveness and safety of PCSK9 inhibitors in a real-life Spanish cohort
Juan Vicente-Valor, Xandra García-González, Sara Ibáñez-García, María Esther Durán-García, Ana de Lorenzo-Pinto, Carmen Rodríguez-González, Irene Méndez-Fernández, Juan Carlos Percovich-Hualpa, Ana Herranz-Alonso, María Sanjurjo-Sáez
Biomedicine & Pharmacotherapy.2022; 146: 112519. CrossRef
Development of small-molecule PCSK9 inhibitors for the treatment of hypercholesterolemia
Shakir Ahamad, Shintu Mathew, Waqas A. Khan, Kishor Mohanan
Drug Discovery Today.2022; 27(5): 1332. CrossRef
The biological relevance of PCSK9: when less is better…
Majambu Mbikay, Michel Chrétien
Biochemistry and Cell Biology.2022; 100(3): 189. CrossRef
Fenofibrate add-on to statin treatment is associated with low all-cause death and cardiovascular disease in the general population with high triglyceride levels
Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
Metabolism.2022; 137: 155327. CrossRef
Homozygous Familial Hypercholesterolemia
Lisa Young, Emily E. Brown, Seth S. Martin
JACC: Case Reports.2022; 4(23): 101666. CrossRef
Familial Hypercholesterolemia and Its Current Diagnostics and Treatment Possibilities: A Literature Analysis
Kristina Zubielienė, Gintarė Valterytė, Neda Jonaitienė, Diana Žaliaduonytė, Vytautas Zabiela
Medicina.2022; 58(11): 1665. CrossRef
Efficacy and Safety of Alirocumab in Children and Adolescents With Homozygous Familial Hypercholesterolemia: Phase 3, Multinational Open-Label Study
Eric Bruckert, Sonia Caprio, Albert Wiegman, Min-Ji Charng, Cézar A. Zárate-Morales, Marie T. Baccara-Dinet, Garen Manvelian, Anne Ourliac, Michel Scemama, Stephen R. Daniels
Arteriosclerosis, Thrombosis, and Vascular Biology.2022; 42(12): 1447. CrossRef

Update on Familial Hypercholesterolemia: Diagnosis, Cardiovascular Risk, and Novel Therapeutics: Sang-Hak Lee; Endocrinol Metab. 2017;32(1):36-40. Published online January 19, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.1.36

4,034 View
57 Download
11 Web of Science
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Abstract PDF PubReader

In recent studies, the reported prevalence of heterozygous familial hypercholesterolemia (FH) has been higher than in previous reports. Although cascade genetic screening is a good option for efficient identification of affected patients, diagnosis using only clinical criteria is more common in real clinical practice. Cardiovascular risk is much higher in FH patients due to longstanding low density lipoprotein cholesterol (LDL-C) burden and is also influenced by other risk factors. Although guidelines emphasize aggressive LDL-C reduction, the majority of patients cannot reach the LDL-C goal by conventional pharmacotherapy. Novel therapeutics such as proprotein convertase subtilisin/kexin type 9 inhibitors have shown strong lipid lowering efficacy and are expected to improve treatment results in FH patients.

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Citations to this article as recorded by

Effectiveness and Safety of a Fixed-Dose Combination of Valsartan and Rosuvastatin (Rovatitan® Tablet) in Patients with Concomitant Hypertension and Hyperlipidemia: An Observational Study
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Drug Design, Development and Therapy.2023; Volume 17: 1047. CrossRef
Role of PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia
Brian Tomlinson, Nivritti Gajanan Patil, Manson Fok, Christopher Wai Kei Lam
Endocrinology and Metabolism.2021; 36(2): 279. CrossRef
Identification and Functional Characterization of a Low-Density Lipoprotein Receptor Gene Pathogenic Variant in Familial Hypercholesterolemia
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Gut Microbiota and Complications of Type-2 Diabetes
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LDLR Gene Mutation p.Asp360His and Familial Hypercholesterolemia in a Mexican Community
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A Rare Double Heterozygous Mutation in Low-Density Lipoprotein Receptor and Apolipoprotein B-100 Genes in a Severely Affected Familial Hypercholesterolaemia Patient
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Cureus.2020;[Epub] CrossRef
Efficacy and Safety of a Fixed-Dose Combination of Candesartan and Rosuvastatin on Blood Pressure and Cholesterol in Patients With Hypertension and Hypercholesterolemia: A Multicenter, Randomized, Double-Blind, Parallel Phase III Clinical Study
Kyoung Im Cho, Bo Hyun Kim, Yong Hyun Park, Jeong-Cheon Ahn, Sang Hyun Kim, Wook Jin Chung, Weon Kim, Il Suk Sohn, Jin Ho Shin, Yong Jin Kim, Kiyuk Chang, Cheol Woong Yu, Soe Hee Ahn, Seok Yeon Kim, Jae Kean Ryu, Jong Young Lee, Bum Kee Hong, Taek Jong Ho
Clinical Therapeutics.2019; 41(8): 1508. CrossRef
Diagnosis and Treatment of Heterozygous Familial Hypercholesterolemia
Mary P. McGowan, Seyed Hamed Hosseini Dehkordi, Patrick M. Moriarty, P. Barton Duell
Journal of the American Heart Association.2019;[Epub] CrossRef
Autosomal recessive hypercholesterolemia: Case report
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Journal of Clinical Lipidology.2019; 13(6): 887. CrossRef
Q192R polymorphism in the PON1 gene and familial hypercholesterolemia in a Saudi population
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Annals of Saudi Medicine.2017; 37(6): 425. CrossRef

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