A Review of PCSK9 Inhibitors and their Effects on Cardiovascular Diseases

Background: Cardiovascular diseases remain the leading cause of morbidity and mortality in the world, with elevated Low-Density Lipoprotein-Cholesterol (LDL-C) levels as the major risk factor. Lower levels of LDL-C can effectively reduce the risk of cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in regulating the degradation of hepatic LDL receptors that remove LDL-C from the circulation. PCSK9 inhibitors are a new class of agents that are becoming increasingly important in the treatment to reduce LDL-C levels. Two PCSK9 inhibitors, alirocumab and evolocumab, have been approved to treat hypercholesterolemia and are available in the United States and the European Union. Through the inhibition of PCSK9 and increased recycling of LDL receptors, serum LDL-C levels can be significantly reduced.

Objective: This review will describe the chemistry, pharmacokinetics, and pharmacodynamics of PCSK9 inhibitors and their clinical effects.