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ISSN 2073-8137

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The lipid-lowering treatment after acute coronary syndrome in the real clinical practice: possible role of the pharmacogenetic interactions

[Original research]
Victoria Brazhnik; Larisa Minushkina; Anastasia Alexandrovna Rogozhina; Anastasia Averkova; Ekaterina Zubova; Olga Koroleva; Marina Chichkova; Niyaz Hasanov; Elena Kosmacheva; Olga Boeva;

The study aimed to assess the possibility of individualizing lipid-lowering therapy in patients after acute coronary syndrome (ACS). The study included 1408 patients from the ORACUL II study, who has undergone ACS for the first time (60.5 % of men, average age 65.18±12.81 years), discharged from the hospital. Statins were prescribed to 1315 (93.4 %) patients at discharge from the hospital. During the first year of observation 778 (55.2 %) patients use statins regularly, 394 (27.9 %) had low adherence to treatment, 236 (16.7 %) refused statins in a month after discharge. Among patients highly adhere to statin treatment, compared with patients without statins or having poor adherence to lipid-lowering therapy, the lower frequency of coronary events (8.1 % and 19.0 % of patients, respectively, p<0.001) was noted and a lower average expected time before coronary outcome (805.9±9.92 vs. 751.3±10.61 days, p=0.002). A significant decrease of statins effect on cardiovascular risk was observed in carriers of A allele of ANXA2 gene, which initially had a higher level of low-density lipoprotein cholesterol than patients without A allele in the genotype (4.18±2.602 mmol/L vs. 3.12±1.197 mmol/L, p=0.017).


1. Ibanez B., James S., Agewall S., Antunes M. J., Bucciarelli-Ducci C. [et al.] ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation:The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur.Heart J. 2018;39(2):119-177. https://doi.org/10.1093/eurheartj/ehx393
2. Mach F., Baigent C., Catapano A. L., Koskinas K. C., Casula M. [et al.] 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur. Heart J.2019;ehz455. https://doi.org/10.1093/eurheartj/ehz455
3. Kotseva K., Wood D., De Bacquer D., De Backer G., Rydén L. [et al.]; EUROASPIRE Investigators. EUROASPIRE IV: A European Society of Cardiology survey on the lifestyle, risk factor and therapeutic management of coronary patients from 24 European countries. Eur. J. Prev. Cardiol. 2016;23(6):636-648. https://doi.org/10.1177/2047487315569401
Nishikido T., Ray K. K. Non-antibody Approaches to Proprotein Convertase Subtilisin Kexin 9 Inhibition: siRNA,Antisense Oligonucleotides, Adnectins, Vaccination, and New Attempts at Small-Molecule Inhibitors Based on New Discoveries. Front. Cardiovasc. Med. 2019;5:199. https://doi.org/10.3389/fcvm.2018.00199
5. Seidah N. G., Poirier S., Denis M., Parker R., Miao B. [et al.] Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation. PLoS One.2012;7(7):e41865. https://doi.org/10.1371/journal.pone.0041865
6. Averkova A. O., Brazhnik.V. A., Koroleva O. S., Zubova E. A., Hasanov N. R. [et al.] Acute coronary syndrome in young patients with familial hypercholesterolemia based on the results of ORACUL II observation trial. Medical news of North Caucasus. 2017;12(1):5-8. https://doi.org/10.14300/mnnc.2017.12001
7. Stone N. J., Robinson J. G., Lichtenstein A. H., Bairey Merz C. N., Blum C. B. [et al.] American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol. 2014;63(25PtB):2889-2934. https://doi.org/10.1016/j.jacc.2013.11.002
8. Besseling J., Kindt I., Hof M., Kastelein J. J., Hutten B. A. [et al.] Severe heterozygous familial hypercholesterolemia and risk for cardiovascular disease: a study of a cohort of 14,000 mutation carriers. Atherosclerosis. 2014;233(1):219-22. https://doi.org/10.1016/j.atherosclerosis.2013.12.020
9. Shalnova S. A., Belov V. N., Valiakhmetov М. N., Veselovskaya N. G., Voronina N. V. [et al.] Approaches to statin therapy adherence improvement. Cardiovascular Therapy and Prevention. 2018;17(2):81-87. http://dx.doi.org/10.15829/1728-8800-2018-2-81-87
10. Rockberg J., Jørgensen L., Taylor B., Sobocki P., Johansson G. Risk of mortality and recurrent cardiovascular events in patients with acute coronary syndromes on high-intensity statin treatment. Prev. Med. Rep. 2017;6:203-209. https://doi.org/10.1016/j.pmedr.2017.03.001
11. Kerr A. J., Turaga M., Grey C., Lee M., McLachlan A. [et al.] Initiation and maintenance of statins and aspirin after acute coronary syndromes (ANZACS-QI 11). J. Prim. Health Care. 2016;8(3):238-249. https://doi.org/10.1071/HC16013
12. Sun Y., Myint P. K., Patel A., Yang X., Li M. [et al.] Sixmonth adherence to Statin use and subsequent risk of major adverse cardiovascular events (MACE) in patients discharged with acute coronary syndromes. Lipids Health Dis. 2017;16(1):155. https://doi.org/10.1186/s12944-017-0544-0
13. Erlikh A. D. on behalf of the RECORD-3 registry workteam.Twelve months outcomes in patients with acute coronary syndrome, by the National Registry RECORD-3. Russ. J.Cardiol. 2018;3(155):23-30. https://doi.org/10.15829/1560-4071-2018-3-23-30
14. Xing Y., Liu J., Hao Y., Liu J., Huo Y. [et al.] CCC-ACS Investigators. Prehospital statin use and low-density lipoprotein cholesterol levels at admission in acute coronary syndrome patients with history of myocardial infarction or revascularization: Findings from the Improving Care for Cardiovascular Disease in China (CCC) project. Am.Heart J. 2019;212:120-128. https://doi.org/10.1016/j.ahj.2019.02.019
15. Dyrbus K., Gasior M., Desperak P., Nowak J., Osadnik T.[et al.] Characteristics of lipid profile and effectiveness of management of dyslipidemia in patients with acute coronary syndromes – Data from the TERCET registry with 19,287 patients. Pharmacol. Res. 2019;139:460-466. https://doi.org/10.1016/j.phrs.2018.12.002
16. Rockberg J., Jørgensen L., Taylor B., Sobocki P.,Johansson G. Risk of mortality and recurrent cardiovascular events in patients with acute coronary syndromes on high intensity statin treatment. Prev. Med. Rep. 2017;6:203-209. https://doi.org/10.1016/j.pmedr.2017.03.001
17. Vale N., Nordmann A. J., Schwartz G. G., de Lemos J.,Colivicchi F. [et al.] Statins for acute coronary syndrome.Cochrane Database Syst. Rev. 2014;(9):CD006870. https://doi.org/10.1002/14651858
18. Shibui T., Nakagomi A., Kusama Y., Atarashi H., Mizuno K. Impact of statin therapy on renal function and longterm prognosis in acute coronary syndrome patients with chronic kidney disease. Int. Heart J. 2010;51(5):312-318.
19. Natanzon S. S., Matetzky S., Beigel R., Iakobishvili Z.,Goldenberg I. [et al.] Acute Coronary Syndrome Israel Survey (ACSIS) investigators. Statin therapy among chronic kidney disease patients presenting with acute coronary syndrome. Atherosclerosis. 2019;286:14-19. https://doi.org/10.1016/j.atherosclerosis.2019.05.002
20. Safaryan V. I., Brazhnik V. A., Minushkina L. O., Averkova A. O., Rogozhina A. A. [et al.] The prognostic value of calcified aortic stenosis in patients with acute coronary syndrome.Kremljovskaya Medicina. Clinichesky Vestnik. 2018;4:8-15.
21. Fairoozy R. H., Cooper J., White J., Giambartolomei C.,Folkersen L. [et al.] UCLEB consortium. Identifying low density lipoprotein cholesterol associated variants in the Annexin A2 (ANXA2) gene. Atherosclerosis. 2017;261:60-68. https://doi.org/10.1016/j.atherosclerosis.2017.04.010
22. Hwang J., Hodis H. N., Hsiai T. K., Asatryan L., Sevanian A. Role of annexin II in estrogen-induced macrophage matrix metalloproteinase-9 activity: the modulating effect of statins. Atherosclerosis. 2006;189(1):76-82. https://doi.org/10.1016/j.atherosclerosis.2005.11.026

Keywords: acute coronary syndrome, statins, adherence, gene ANXA2

Stavropol State Medical Academy
Pyatigorsk State Research Institute of Balneotherapeutics
Pyatigorsk State Pharmaceutical Academy