Cardiovascular Outcomes of PCSK9 Inhibitors: With Special Emphasis on Its Effect beyond LDL-Cholesterol Lowering

Abstract EN

PCSK9 inhibitors, monoclonal antibodies, are novel antihypercholesterolemic drugs.

FDA first approved them in July 2015.

PCSK9 protein (692-amino acids) was discovered in 2003.

It plays a major role in LDL receptor degradation and is a prominent modulator in low-density lipoprotein cholesterol (LDL-C) metabolism.

PCSK9 inhibitors are monoclonal antibodies that target PCSK9 protein in liver and inhibiting this protein leads to drastically lowering harmful LDL-C level in the bloodstream.

Despite widespread use of the statin, not all the high-risk patients were able to achieve targeted level of LDL-C.

Using PCSK9 inhibitors could lead to a substantial decrement in LDL-C plasma level ranging from 50% to 70%, either as a monotherapy or on top of statins.

A large number of trials have shown robust reduction of LDL-C plasma level with the use of PCSK9 inhibitors as a monotherapy or in combination with statins in familial and nonfamilial forms of hypercholesterolemia.

Moreover, PCSK9 inhibitors do not appear to increase the risk of hepatic and muscle-related side effects.

PCSK9 inhibitors proved to be a highly potent and promising antihypercholesterolemic drug by decreasing LDL-R lysosomal degradation by PCSK9 protein.

Statin drugs are known to have some pleiotropic effects.

In this article, we are also focusing on the effects of PCSK9 inhibitor beyond LDL-C reduction like endothelial inflammation, atherosclerosis, its safety in patients with diabetes, obesity, and chronic kidney disease, and its influence on neurocognition and stroke.