Possibilities of correction of hyperlipoproteidemia (a) by PCSK9-targeted therapy in patients with very high cardiovascular risk
https://doi.org/10.21626/vestnik/2025-1/04
EDN: JKGVNQ
Abstract
Objective - to evaluate the possibilities of correcting hyperlipoproteidemia (a) in patients with very high cardiovascular risk (SSR) during the use of combined lipid-lowering therapy with PCSK9 inhibitors.
Materials and methods. The present study included 66 patients with ischemic heart disease with very high SSR who did not reach the target ranges of low-density lipoprotein cholesterol (LDL cholesterol) during long-term optimal lipid-lowering therapy. All patients were prescribed a combination of statin, ezetimibe and alirocumab for a duration of 6 months. During treatment, the concentration of lipoprotein (a) (Lp(a)), LDL cholesterol and high-density lipoprotein cholesterol was determined at 6 visits.
Results. A statistically significant decrease in Lp(a) concentration by 21.8% was shown from 22.75 [6.58; 34.78] mg/dl to 17.93 [6.03; 28.31] mg/dl (p<0.001) during therapy. Hyperlipoproteidemia (a) at the screening stage was registered in 40.91% of patients. The target values of LDL cholesterol were reached by 71.21% of the study participants (n=47). LDL cholesterol decreased by 63.21% from 3.86±0.71 mmol/l to 1.42±0.31 mmol/l (p<0.001), high-density lipoprotein cholesterol increased by 30% from 0.7±0.09 mmol/l to 0.91±0.06 mmol/l (p<0.001).
Conclusion. The use of combined lipid-lowering therapy with alirocumab makes it possible to achieve a significant decrease in the concentration of Lp(a) in patients with very high SSR. However, the use of this treatment regimen is possible only in patients who have not reached the target values of LDL cholesterol against the background of long-term optimal lipid-lowering therapy.
About the Authors
Andrei A. Kuznetsov
Russian Scientific Center of Radiology (RNCRR);
Kursk State Medical University (KSMU)
Russian Federation
Russian Federation
Galina S. Mal
Kursk State Medical University (KSMU)
Russian Federation
Russian Federation
Dr. Sci. (Med.), Professor, Head of the Department of Pharmacology, KSMU, Kursk, Russian Federation
Elena Yu. Puchkova
References
1. Roth G.A., Mensah G.A., Fuster V. The Global Burden of Cardiovascular Diseases and Risks: A Compass for Global Action. J Am Coll Cardiol. 2020;76(25): 2980-2981. DOI: 10.1016/j.jacc.2020.11.021.
2. Langsted A., Madsen C.M., Nordestgaard B.G. Contribution of remnant cholesterol to cardiovascular risk. Journal of internal medicine. 2020;288(1):116-127. DOI: 10.1111/joim.13059.
3. Jawi M.M., Frohlich J., ChanS.Y. Lipoprotein (a) the Insurgent: A New Insight into the Structure, Function, Metabolism, Pathogenicity, and Medications Affecting Lipoprotein (a) Molecule. J Lipids. 2020;2020:3491764. DOI: 10.1155/2020/3491764.
4. Wilson D., Jacobson T., Jones P., Koschinsky M., McNeal C., Nordestgaard B., Orringer C. Use of Lipoprotein(a) in clinical practice: A biomarker whose time has come. A scientific statement from the National Lipid Association. J Clin Lipid. 2019;13(3):374-392. DOI: 10.1016/j.jacl.2019.04.010.
5. Nordestgaard B.G., Langsted A. Lipoprotein (a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology. Journal of lipid research. 2016;57(11):1953-1975. DOI: 10.1194/jlr.R071233.
6. Liu S.L., Rozi R., Shi H.W., Gao Y., Guo Y., Tang Y., Li J., Wu N. Association of serum lipoprotein(a) level with the severity and prognosis of calcific aortic valve stenosis: a Chinese cohort study. J Geriatr Cardiol. 2020;17(3):133-140. DOI: 10.11909/j.issn.1671-5411.2020.03.009.
7. Tsimikas S.A. Test in Context: Lipoprotein(a). Journal of the American College of Cardiology. 2017;69(6): 692-711. DOI: 10.1016/j.jacc.2016.11.042.
8. Bjornson E., Adiels M., Taskinen M.R., Burgess S., Chapman M.J., Packard C.J., Boren J. Lipoprotein(a) Is Markedly More Atherogenic Than LDL: An Apolipoprotein B-Based Genetic Analysis. J Am Coll Cardiol. 2024;83(3):385-395. DOI: 10.1016/j.jacc.2023.10.039.
9. Ward N.C., Kostner K., Sullivan D.R., Nestel P., Watts G.F. Molecular, population, and clinical aspects of lipoprotein(a): a bridge too far? Journal of clinical medicine. 2019;12(8):1-23. DOI: 10.3390/jcm8122073.
10. Tsimikas S., Fazio S., Ferdinand K.C., Ginsberg H.N., Koschinsky M.L., Marcovina S.M., Moriarty P.M., Rader D.J., et al. NHLBI Working Group Recommendations to Reduce Lipoprotein(a)-Mediated Risk of Cardiovascular Disease and Aortic Stenosis. J Am Coll Cardiol. 2018;71(2): 177-192. DOI: 10.1016/j.jacc.2017.11.014.
11. Hu P., Dharmayat K.I., Stevens C., Sharabiani M., Jones R.S., Watts G.F., Genest J., Ray K.K., Vallejo-Vaz A.J. Prevalence of Familial Hypercholesterolemia Among the General Population and Patients With Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analysis. Circulation. 2020;141(22):1742-1759. DOI: 10.1161/CIRCULATIONAHA.119.044795.
12. Shalnova S.A., Yezhov M.V., Metelskaya V.A., Evstifeeva S.E., Tarasov V.I., Muromtseva G.A., Balanova Yu.A., Imaeva A.E., et al. Association of lipoprotein (a) with risk factors for atherosclerosis in the Russian population (data from the ESSE-RF Observational Study). Rational pharmacotherapy in cardiology. 2019;15(5):612-621 (in Russ.). DOI: 10.20996/1819-6446-2019-15-5-612-621. EDN: KBMFPI.
13. Kronenberg F., Mora S., Stroes E.S., Ference B.A., Arsenault B.J., Berglund L., Dweck M.R., Koschinsky M., et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43(39):3925-3946. DOI: 10.1093/eurheartj/ehac361.
14. Mach F., Baigent C., Catapano A.L., Koskinas K.C., Casula M., Badimon L., Chapman M.J., Backer G.G., et al. ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies. 2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Atherosclerosis. 2019;290:140-205. DOI: 10.1016/j.atherosclerosis.2019.08.014.
15. Ezhov M.V., Kukharchuk V.V., Sergienko I.V., Alieva A.S., Anciferov M.B., Ansheles A.A., Arabidze G.G., Aronov D.M., et al. Disorders of lipid metabolism. Clinical guidelines 2023.Russian Journal of Cardiology. 2023;28(5):5471 (in Russ.). DOI: 10.15829/1560-4071-2023-5471. EDN: YVZOWJ.
16. Wright R.S., Ray K.K., Raal F.J., Kallend D.G., Jaros M., Koenig W., Leiter L.A., Landmesser U., et al. ORION Phase III Investigators. Pooled Patient-Level Analysis of Inclisiran Trials in Patients With Familial Hypercholesterolemia or Atherosclerosis. J Am Coll Cardiol. 2021;77(9):1182-1193. DOI: 10.1016/j.jacc.2020.12.058.
17. Raal F.J., Kallend D., Ray K.K., Turner T., Koenig W., Wright R.S., Wijngaard P.L., Curcio D., et al. ORION-9 Investigators. Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia. N Engl J Med. 2020;382(16):1520-1530. DOI: 10.1056/NEJMoa1913805.
18. Ray K.K., Wright R.S., Kallend D., Koenig W., Leiter L.A., Raal F.J., Bisch J.A., Richardson T., et al. ORION-10 and ORION-11 Investigators. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020;382(16):1507-1519. DOI: 10.1056/NEJMoa1912387.
19. Gaudet D., Watts G.F., Robinson J.G., Minini P., Sasiela W.J., Edelberg J., Louie M.J., Raal F.J. Effect of Alirocumab on Lipoprotein(a) Over ≥1.5 Years (from the Phase 3 ODYSSEY Program). Am J Cardiol. 2017;119(1):40-46. DOI: 10.1016/j.amjcard.2016.09.010.
20. Barbarash O.L., Karpov Yu.A., Kashtalap V.V., Boschenko A.A., Ruda M., Akchurin R.S., Alekyan B.G., Aronov D.M., et al. Stable ischemic heart disease. Clinical guidelines 2020.Russian Journal of Cardiology. 2020;25(11):4076 (in Russ.). DOI: 10.15829/1560-4071-2020-4076. EDN: THCMQS.
21. Nordestgaard B.G., Chapman M.J., Ray K., Boren J., Andreotti F., Watts G.F., Ginsberg H., Amarenco P., et al. European Atherosclerosis Society Consensus Panel. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31(23):2844-2853. DOI: 10.1093/eurheartj/ehq386.
22. Fernandez-Prado R., Perez-Gomez M.V., Ortiz A. Pelacarsen for lowering lipoprotein(a): implications for patients with chronic kidney disease. Clin Kidney J. 2020;13(5):753-757. DOI: 10.1093/ckj/sfaa001.
23. Donoghue M.L., Lopez J.A., Knusel B., Gencer B., Wang H., Wu Y., Kassahun H., Sabatine M.S. Study design and rationale for the Olpasiran trials of Cardiovascular Events And lipoproteiN(a) reduction-DOSE finding study (OCEAN(a)-DOSE). Am Heart J. 2022;251:61-69. DOI: 10.1016/j.ahj.2022.05.004.
24. Nissen S.E., Linnebjerg H., Shen X, Wolski K., Ma X., Lim S., Michael L.F., Ruotolo G., et al. Lepodisiran, an Extended-Duration Short Interfering RNA Targeting Lipoprotein(a): A Randomized Dose-Ascending Clinical Trial. JAMA. 2023;330(21):2075-2083. DOI: 10.1001/jama.2023.21835.
25. Wu M.F., Xu K.Z., Guo Y.G., Yu J., Wu Y., Lin L.M. Lipoprotein (a) and atherosclerotic сardiovascular disease: Current understanding and future perspectives. Cardiovasc Drugs Ther. 2019;33(6): 739-748. DOI: 10.1007/s10557-019-06906-9.
26. Marcovina S.M., Koschinsky M.L., Albers J.J., Skarlatos S. Report of the National Heart, Lung, and Blood Institute Workshop on lipoprotein (a) and cardiovascular disease: recent advances and future directions. Clinical Chemistry. 2003;49(11):1785-1796. DOI: 10.1373/clinchem.2003.023689.
27. Yezhov M.V., Safarova M.S., Matchin Yu.G., Soboleva D.I., Afanasyeva O.I., Pokrovsky S.N. The relationship of high lipoprotein (a) levels with coronary artery patency during the first year after percutaneous coronary interventions. The clinician. 2011;(1):18-24 (in Russ.). DOI: 10.17650/1818-8338-2011-1-18-23.
28. Kuznetsov A.A., Mal G.S., Manuilov V.M. Prevalence of hyperlipoproteidemia (a) in patients with very high cardiovascular risk. Atherosclerosis and dyslipidemia. 2024;3(56):45-51 (in Russ.). DOI: 10.34687/2219-8202.JAD.2024.03.0004. EDN: WYXMGL.
29. Kamstrup P.R., Benn M., Tybjaerg-Hansen A., Nordestgaard B.G. Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: the Copenhagen City Heart Study. Circulation. 2008;117(2):176-84. DOI: 10.1161/CIRCULATIONAHA.107.715698.
30. Mal G.S., Kuznetsov A.A. Ischemic heart disease and chronic kidney disease: the possibilities of PCSK9 inhibitors in achieving the target values of atherogenic lipoproteins. Innovative medicine of Kuban. 2022;(2):14-21 (in Russ.). DOI: 10.35401/2541-9897-2022-25-2-14-21. EDN: XKWNPY.
31. Kuznetsov A.A., Mal G.S. Dynamics of changes in lipoproteins and estrogens in the process of drug correction of dyslipidemia with PCSK9 inhibitors with various comorbid pathology.International Journal of Heart and Vascular Diseases. 2022;10(35):23-32 (in Russ.). DOI: 10.24412/2311-1623- 2022-35-23-32.
32. Kuznetsov A.A., Mal G.S. The possibilities of using PCSK9 inhibitors in patients with coronary heart disease in combination with type 2 diabetes mellitus. Regional blood circulation and microcirculation. 2022;21(2):16-25 (in Russ.). DOI: 10.24884/1682-6655-2022-21-2-16-25. EDN: CTOLSR.
Review
For citations:
Kuznetsov A.A., Mal G.S., Puchkova E.Yu. Possibilities of correction of hyperlipoproteidemia (a) by PCSK9-targeted therapy in patients with very high cardiovascular risk. Humans and their health. 2025;28(1):31-40. (In Russ.) https://doi.org/10.21626/vestnik/2025-1/04. EDN: JKGVNQ
Views:
122
Email this article 