South African Family Practice

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The role of proprotein convertase subtilisin/kexin type 9 inhibitors in managing cardiovascular risk

Natalie Schellack, Gustav Schellack, E Bronkhorst


Hypercholesterolaemia and dyslipidaemia, marked by decreased levels of high-density lipoprotein and elevated levels of lowdensity lipoprotein (LDL), increase the risk of cardiovascular disease. Familial hypercholesterolaemia (FH), diagnosed based on the clinical features seen in patients with a positive family history, constitutes a heritable disorder involving a single gene. FH can exist in either the heterozygous or homozygous form, and may be differentiated based on clinical features and genetic studies. A novel drug target, proprotein convertase subtilisin/kexin type 9 (PCSK9), has resulted in the development and subsequent approval of new, targeted monoclonal antibodies in the treatment of FH. Targeting PCSK9 with monoclonal antibodies, i.e. evolocumab and alirocumab, inhibits the degradation of LDL receptors, and against a background of optimised statin therapy, increases the life expectancy of patients with hypercholesterolaemia by reducing the incidence and severity of coronary artery disease.

Keywords: alirocumab, evolocumab, cardiovascular risk factors, familial hypercholesterolaemia, PCSK9, proprotein convertase subtilisin/kexin type 9, LDL cholesterol, LDL receptor

AJOL African Journals Online