Abstract
Dyslipidemia is a disease of abnormal lipid levels in the blood that contributes to the atherosclerotic process. This atherogenic process leads to the formation of plaque and also leads to thromboembolic events and other vascular accidents. It is known that high-density lipoprotein cholesterol serves as a protective effect on the vessel wall and causes the reduction in the progression of atherosclerosis. And multiple interventions are directed in maintaining a higher level of the aforementioned lipoprotein cholesterol. While the low-density lipoprotein stays controversial but lowering its levels through various therapeutic agents is the main goal in the management of dyslipidemia. A newer group of drugs, PCSK9 inhibitors lowers the levels of low-density lipoprotein through modulating PCKS9 gene involved in cholesterol metabolism and affects the levels of the lipoproteins by controlling the receptors. The inhibitors of this gene decrease PCSK9-induced low-density lipoprotein receptor degradation in the lysosomes of hepatocytes increasing its recycling and expression on the cell surface, causing increased clearance of low-density lipoprotein from the circulation. These drugs Alicuromab, Evolocumab and along with other agents can be a novel approach in controlling dyslipidemic state. This review revisits the literature in understanding the pathophysiology of dyslipidemia along with its management by PCKS9 inhibitors, its mechanism of action, its pharmacokinetics, the results of the clinical trials and the limitations in its application.
Highlights
Atherosclerosis is a chronic inflammatory disease of the walls of large and medium-sized arteries
It is known that high-density lipoprotein cholesterol serves as a protective effect on the vessel wall and causes the reduction in the progression of atherosclerosis
A newer group of drugs, proprotein convertase subtilisin/kexin type 9 inhibitors lowers the levels of low-density lipoprotein through modulating proprotein convertase subtilisin/kexin type 9 gene involved in cholesterol metabolism and affects the levels of the lipoproteins by controlling the receptors
Summary
Atherosclerosis is a chronic inflammatory disease of the walls of large and medium-sized arteries. An additional clinical trial was conducted with 968 subjects who all had a history of cardiovascular disease They were divided into two groups at random and one was given the PCSK9 inhibitor Evolocumab while the other group was assigned a placebo. One of the chief advantages of PCSK9 inhibitors is its usage in therapy for familial hypercholesterolemia in people overly sensitive to statins and in people whose low-density lipoprotein-cholesterol LDL-C levels remain high even after they have been put on the maximum dose of statins that can be safely prescribed. Information collected from various clinical trials which assessed Evolocumab and Alirocumab has displayed that individuals on PCSK9 inhibitor therapy have exhibited a greater amount of side effects involving cognitive ability [36, 50]
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