PCSK9 inhibitors - clinical applications

Abstract

The enzyme PCSK9 has an important role in regulating low-density lipoprotein (LDL) receptors and concentrations of LDL cholesterol. Inhibiting this enzyme could therefore reduce the incidence of ischaemic heart disease. The monoclonal antibodies alirocumab, evolocumab and bococizumab are directed against PCSK9 and inhibit its activity. Phase II trials have shown alirocumab and evolocumab to be effective at lowering LDL cholesterol. Preliminary results of these phase II trials show potential benefits in ischaemic heart disease. Reports of adverse effects, including muscular symptoms and neurocognitive changes, were low. Large phase III cardiovascular outcome trials of these monoclonal antibodies will determine their safety and efficacy. These drugs may have a role in the management of patients at very high risk of cardiovascular events such as those with familial hypercholesterolaemia. Show more