Hypolypidemic therapy in the XXI century: what is new?

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Abstract

Relevance. The leading position in mortality throughout the world is occupied by cardiovascular diseases, caused be atherosclerosis process. Statins used to be the gold standard of lipid-lowering therapy for a long time due to their high efficacy, optimal tolerance and safety. Nowadays it has been proved that statins reduce low-density lipoprotein levels in high doses by more than 50 %, in medium doses for about 30–49 %. However, often achieving the target level of lipoproteins is not possible due to a variety of reasons, what became a motivation for creating new drugs. The evidence base for the newest lipid-lowering drugs, some of which have already been approved for clinical use according to the publications in the scientific databases Scopus, PubMed, Web of Science for last 10 years. Main results of the most significant clinical trials of drugs’ effectiveness and safety are described including medicines: alirocumab, inclisiran, bococizumab, pelacarsen, mipomersen, bempedoic acid, lomitapide, evinocumab and also methods of therapeutic lipoprotein apheresis. Dyslipidemia pathogenetic points are considered like inhibition of proprotein convertase subtilisin-kexin type 9, suppression of genes synthesizing lipoprotein (a) by antisense oligonucleotides, cholesterol synthesis suppression by inactivation of adenosine triphosphate-citrate lyase enzyme; the action of microsomal inhibitors of triglyceride transfer protein. Conclusion. Searching for new lipid-lowering rational regimens is still ongoing, therefore it is necessary to carefully analyze effectiveness and safety profile for the newest drugs. Some of them like inhibition of proprotein convertase subtilisin-kexin type 9 are actively used in medicine today, while others, the most promising, will be in the future. Ensuring of atherogenic lipoproteins complete control will subsequently make a significant contribution to the primary and secondary cardiovascular diseases prevention, which will save many human lives.

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Table 1 Drugs from the group of iPCSK9, registered in Russia

Title

Structure

Release form

Dosage

Contraindications

Evolocumab

monoclonal antibody

single-dose prefilled autoinjector; 140 mg per в 1 ml

the usual dose is either 140 mg every 2 weeks or 420 mg once a month

the patient’s age is under 18 years with heterozygous hypercholesterolemia; age up to 12 years with homozygous hypercholesterolemia

Alirocumab

monoclonal antibody

single-dose prefilled

autoinjector; 75 mg per

1 ml;

150 mg per 1 мл

the recommended dose is 75–150 mg once every 2 weeks administered subcutaneously, or 300 mg once every 4 weeks

individual hypersensitivity, pregnancy and lactation, children under 18 years of age.

Inclisiran

small interfering ribonucleic acid (siRNA)

prefilled syringe; 284 mg per 1,5 ml;

The recommended dose of Leqvio is 284 mg administered as a single subcutaneous injection: initially, again at 3 months, followed by every 6 months

hypersensitivity to the drug

Fig.1. The Scheme of cholesterol synthesis inhibiting by bempedoic acid Bempedoic acid blocks the action of the enzyme ATP citrate lyase, which prevents the conversion of citrate to acetyl-­CoA that inhibits cholesterol synthesis. By comparison, statins are involved in inhibiting of cholesterol synthesis a little bit later

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About the authors

Natalya Yu. Ob’edkova

Kursk State Medical University

Author for correspondence.
Email: obedkovany@kursksmu.net
ORCID iD: 0000-0003-2072-5511
SPIN-code: 7700-0707
Kursk, Russian Federation

Diana N. Usacheva

Kursk State Medical University

Email: obedkovany@kursksmu.net
ORCID iD: 0009-0005-7029-2541
Kursk, Russian Federation

Galina S. Mal

Kursk State Medical University

Email: obedkovany@kursksmu.net
ORCID iD: 0000-0001-6290-1195
SPIN-code: 4371-7708
Kursk, Russian Federation

Evgenij G. Ob’edkov

Kursk State Medical University

Email: obedkovany@kursksmu.net
ORCID iD: 0000-0003-0566-1476
Kursk, Russian Federation

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1. Fig.1. The Scheme of cholesterol synthesis inhibiting by bempedoic acid Bempedoic acid blocks the action of the enzyme ATP citrate lyase, which prevents the conversion of citrate to acetyl-CoA that inhibits cholesterol synthesis. By comparison, statins are involved in inhibiting of cholesterol synthesis a little bit later

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