Abstract
High plasma levels of low density lipoproteins (LDLs) represent one of the major risk factors for cardiovascular disease, as shown by many epidemiological studies. On the other hand, randomized trials designed to address the clinical impact of lipid lowering interventions, have clearly shown that reduction in LDL plasma levels lead to a significant decrease in major cardiovascular events. Based on these observations, pharmacological modulation of LDLs has been highly investigated. Statins, alone or in combination, represent the most powerful agents to date available to reach the LDLs levels suggested by the current guidelines. However, in some patients the recommended LDL reduction is difficult to be achieved because of genetic background (familial hypercholesterolemia), side effects (statin intolerance), or simply because of a non-sufficient response. In the last few years, our understanding of the basic mechanisms involved in the lipoprotein metabolism has progressed significantly. The crucial role of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged. The main characterized function of PCSK9 relates to the binding to LDL-C receptors (LDLR) in hepatocytes. However, PCSK9 does not interfere with the binding between LDL and its own receptor, but with the ability of the latest to return to the surface of the hepatocyte and bind new LDL molecules. Based on these observations, blocking PCSK-9 may reduce the LDLR clearance, thus increasing the ability of LDLR to remove circulating LDLs. Pharmacological inhibition of this protein has been proposed as new therapeutic approach. The clinical evidence available to date seem to fully support this hypothesis.
Highlights
Several epidemiological studies have clearly shown the existence of a tight correlation between lipid levels in blood and atherosclerotic cardiovascular disease (CVD) [1]
Treatment is highly recommended for people with hyperlipidemia [4]
In the ODYSSEY MONO, alirocumab has been shown to be more powerful than ezetimibe in reducing low density lipoproteins (LDLs) cholesterol (47% vs. 16%) in 103 hypercolesterolemic patients with cardiovascular disease [65]
Summary
Several epidemiological studies have clearly shown the existence of a tight correlation between lipid levels in blood and atherosclerotic cardiovascular disease (CVD) [1]. Acute thrombus formation superimposed on a preexisting plaque and the subsequent blood flow reduction is responsible for the conversion of atherosclerosis from a chronic disease to an acute medical emergency, such as acute coronary syndromes (ACS), stroke and related problems [3] Because of this risk, treatment is highly recommended for people with hyperlipidemia [4]. The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) in 2003 [11] opened a new molecular and therapeutical scenario This protein is a crucial factor in the clearance pathway of low-density lipoproteins (LDLs) and its inhibition appears to be highly effective in reducing LDLs levels. This review will discuss the available data on the safety and effectiveness of PCSK9 inhibition starting from the biological mechanisms to its role in the clinical setting
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
