PCSK9 inhibitors

What are PCSK9 inhibitors?

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme that binds to low-density lipoprotein receptors (LDL receptors), which stops LDL being removed from the blood, leading to an increase in blood levels of LDL. The PCSK9 inhibitor blocks the PCSK9 enzyme, resulting in more LDL receptors available to remove LDL from the blood, which produces in a decrease in LDL blood levels.

PCSK9 inhibitors are a new class of drugs that lower low-density lipoprotein (LDL), or “bad,” cholesterol. PCSK9 inhibitors are set to revolutionize the management of atherosclerotic risk. There are two FDA-approved medications: alirocumab (Praluent) and (Repatha).

The Food and Drug Administration (FDA) has approved two types of PCSK9 inhibitors:

Alirocumab (Praluent®).
Evolocumab (Repatha®).

Inhibition of secreted PCSK9 should therefore increase the number of available LDLRs on the cell surface and increase uptake of LDL‐C into the cell. PCSK9 inhibition thus offers a novel therapeutic mechanism for the lowering of LDL‐C levels.

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Single Domain Antibodies Are Potent Inhibitors of Low Density Lipoprotein Receptor Degradation.

The enzyme PCSK9 causes liver cells to remove more LDL (the “bad” cholesterol) from the bloodstream. Importantly, PCSK9 inhibitors don’t have the mild anti-clotting effects that statins seem to have. It’s this anti-clotting effect that could lead to a higher risk of bleeding in the brain.