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PCSK9 inhibitors: an overview on a new promising lipid-lowering therapy


Denegri, Andrea; Petrova-Slater, Iveta; Pasotti, Elena; Rossi, Maria Grazia; Pedrazzini, Giovanni Battista; Moccetti, Tiziano; Moccetti, Marco (2016). PCSK9 inhibitors: an overview on a new promising lipid-lowering therapy. Journal of Cardiovascular Medicine, 17(4):237-244.

Abstract

Atherosclerosis is characterized by cholesterol deposition in the arterial intima, with subsequent plaque formation and arterial disease. Low-density lipoprotein cholesterol (LDL-C) plays the most important role in the atherogenesis process, which is the substrate of cardiovascular disease and is the leading cause of death worldwide. Several studies show that a strict control of risk factors, particularly the reduction of LDL-C levels, is a cornerstone in primary and secondary prevention of coronary heart disease. Statins are currently the most effective drugs for lowering LDL-C, but the discovery of proprotein convertase subtilisin kexin 9 (PCSK9) has opened up new therapeutic options in lipid management. PCSK9 reduces LDL-receptors' recycling resulting in a decrease of LDL-C receptors on the surface of hepatocytes and an increase of LDL-C levels in plasma. Obviously, inhibition of PCSK9 has been associated with an increase of LDL-C receptors with subsequent lowering of plasma levels of LDL-C. The clinical development of monoclonal antibodies against PCSK9 has been achieved through phase I and II studies, and nowadays there are many ongoing phase III trials with promising preliminary results. The aim of this review is to update the evidence for PCSK9 monoclonal antibodies, such as evolocumab, alirocumab and bococizumab, in LDL-C management and to discuss their therapeutic perspectives based on the most recent clinical studies, with attention to side-effects.

Abstract

Atherosclerosis is characterized by cholesterol deposition in the arterial intima, with subsequent plaque formation and arterial disease. Low-density lipoprotein cholesterol (LDL-C) plays the most important role in the atherogenesis process, which is the substrate of cardiovascular disease and is the leading cause of death worldwide. Several studies show that a strict control of risk factors, particularly the reduction of LDL-C levels, is a cornerstone in primary and secondary prevention of coronary heart disease. Statins are currently the most effective drugs for lowering LDL-C, but the discovery of proprotein convertase subtilisin kexin 9 (PCSK9) has opened up new therapeutic options in lipid management. PCSK9 reduces LDL-receptors' recycling resulting in a decrease of LDL-C receptors on the surface of hepatocytes and an increase of LDL-C levels in plasma. Obviously, inhibition of PCSK9 has been associated with an increase of LDL-C receptors with subsequent lowering of plasma levels of LDL-C. The clinical development of monoclonal antibodies against PCSK9 has been achieved through phase I and II studies, and nowadays there are many ongoing phase III trials with promising preliminary results. The aim of this review is to update the evidence for PCSK9 monoclonal antibodies, such as evolocumab, alirocumab and bococizumab, in LDL-C management and to discuss their therapeutic perspectives based on the most recent clinical studies, with attention to side-effects.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Cardiocentro Ticino
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:April 2016
Deposited On:08 Dec 2016 09:49
Last Modified:01 May 2017 00:00
Publisher:Lippincott Williams & Wilkins
ISSN:1558-2027
Publisher DOI:https://doi.org/10.2459/JCM.0000000000000360
PubMed ID:26855411

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