Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9): Impact of PCSK9 on Major Adverse Cardiac and Cerebrovascular Events

Statins are the most widely prescribed drugs to reduce serum low density lipoprotein cholesterol (LDL-C) by inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. LDL-C reduction is associated with a decreased risk of atherosclerotic cardiovascular disease (ASCVD), including cardiovascular disease (CVD) and stroke. Statins reduce LDL-C by 30 to 40%, and the combination with other lipid-lowering agents such as ezetimibe leads to a further reduction by 20 to 25%. However, even the combination of these two agents might not be sufficient in high risk patients to require aggressive LDL-C reduction. Therefore, starting from observations on individuals with loss-of-function in proprotein convertase subtilisin/kexin type 9 (PCSK9), which was associated with lower LDL-C levels and CVD rates, monoclonal antibodies (mAbs) against PCSK9 were developed. To date, two mAbs, alirocumab and evolocumab, have received approval by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). In the present review we give an overview about pathophysiological and clinical aspects as well as evidence for these drugs with respect to cerebrovascular events.