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KMID : 1141520210360020279
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Endocrinology and Metabolism
2021 Volume.36 No. 2 p.279 ~ p.295
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Role of PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia
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Tomlinson Brian
Patil Nivritti Gajanan
Fok Manson
Lam Christopher Wai Kei
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Abstract
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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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KEYWORD
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Alirocumab, Evolocumab, Hydroxymethylglutaryl-CoA reductase inhibitors, Hyperlipoproteinemia type II, PCSK9 protein, human, RNA, small interfering
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