Lipoprotein(a) lowering and cardiovascular risk reduction by PCSK9 inhibitors

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition augments recirculation of the low-density lipoprotein (LDL) receptor to the hepatocyte surface [1], thereby lowering atherogenic particles through accelerated clearance of circulating LDL cholesterol (LDL-C). This observation led to several strategies to inhibit PCSK9, including monoclonal antibodies (evolocumab and alirocumab), small-molecule inhibitors specific to PCSK9, small interfering RNA (siRNA) molecules (inclisiran), antisense oligonucleotides, immunotherapy with a PCSK9 peptide vaccine, and CRISPR/Cas9 editing of PCSK9.