Safety of combined hypolypidemic therapy in clinical practice

Relevance. Atherogenic dyslipidemia is a key factor in the development of atherosclerotic cardiovascular diseases, which for many years remain the leading cause of mortality worldwide. Cardiovascular mortality can be reduced and prevented by correcting modifiable risk factors, in particular by eliminating hypercholesterolemia.

Purpose of the study. To evaluate treatment adherence, side effects and negative events of triple cholesterol-lowering therapy.

Materials and methods. Alirocumab therapy at a dose of 150 mg/ml once every 2 weeks for 3 months was performed in 103 patients living in the Moscow region with atherogenic dyslipidemia. All patients had a high or very high cardiovascular risk group. Before starting alirocumab therapy, patients received monotherapy with atorvastatin at a dose of 40–80 mg or combination therapy with atorvastatin in combination with ezetimibe or fenofibrate.

Results. A decrease in total cholesterol and LDL cholesterol with additional alirocumab therapy was observed in all 103 patients. No exacerbations of coronary heart disease, new cases of acute cerebrovascular accident and transient ischemic attacks were registered. No negative dynamics in the glycemic profile of patients with type 2 diabetes mellitus was revealed. The treatment was not accompanied by obvious adverse reactions and complications.

Conclusion. A three-month course of triple lipid-lowering therapy was characterized by high patient adherence to treatment, good tolerance and no complications. Combined lipid-lowering therapy contributed to the clinical stabilization of coronary heart disease, did not have a negative impact on the course of diabetes mellitus, and was not accompanied by adverse reactions. 

1. 1 Strategy for the Development of Healthcare in the Russian Federation until 2025. Decree of the President of the Russian Federation of June 6, 2019 No. 254. Moscow, 2019. (In Russ.)

2. 2 Ezhov M.V., Bliznyuk S.A., Alekseeva I.A., Vygodin V.A. Prevalence of hypercholesterolemia and statin use in outpatient practice in the Russian Federation. The ICEBERG study – diagnosis of patients with hypercholesterolemia in outpatient practice at an early stage in order to improve cardiovascular prognosis. Atherosclerosis and dyslipidemia. 2017;4(29):5–17. (In Russ.)

3. 3 Piepoli M.F., Hoes A.W., Agewall S., et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016;37(29):2315-2381. https://doi.org/ 10.1093/eurheartj/ehw106

4. 4 Mach F., Baigent C., Catapano A.L., et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. EurHeartJ. 2019. https://doi.org/10.1093/eurheartj/ehz455

5. 5 Ezhov M.V., Sergienko I.V., Aronov D.M. et al. Diagnostics and correction of lipid metabolism disorders for the prevention and treatment of atherosclerosis. Atherosclerosis and dyslipidemia. 2017;3:5-22. (In Russ.)

6. 6 Clinical guidelines – Lipid metabolism disorders – 2023–2024–2025 (15.02.2023) – Approved by the Ministry of Health of the Russian Federation. (adverse effects). (In Russ.)

7. 7 Bichurin D.R., Atmaikina O.V., Cherepanova O.A. Cardiovascular diseases. Regional aspect. International research journal. 2023;8(134). (In Russ.)

8. 8 Yakshina A.D. Cardiovascular diseases in Russia: a review of statistics. Science through the prism of time. 2024;1(82). (In Russ.)

9. 9 Клинические рекомендации – Артериальная гипертензия у взрослых – 2020-2021-2022 (20.01.2023) – Утверждены Минздравом РФ. Clinical guidelines – Arterial hypertension in adults – 2020–2021–2022 (01/20/2023) – Approved by the Ministry of Health of the Russian Federation. (In Russ.)

10. 10 Meijboom W.B., Meijs M.F., Schuijf J.D., etal. Diagnostic accuracy of 64-slice computed tomography coronary angiography: a prospective, multicenter, multivendor study. J Am CollCardiol. 2008;52(25):2135-2144. https://doi.org/10.1016/j.jacc.2008.08.058

11. 11 Stein J.H., Korcarz C.E., Hurst R.T., et al. Use of Carotid Ultrasound to Identify Subclinical Vascular Disease and Evaluate Cardiovascular Disease Risk: A Consensus Statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force Endorsed by the Society for Vascular Medicine. Journal of the American Society of Echocardiography. 2008;21(2):93-111. https://doi.org/10.1016/j.echo.2007.11.011

12. 12 Vlachopoulos C., Xaplanteris P., Aboyans V., et al. The role of vascular biomarkers for primary and secondary prevention.A position paper from the European Society of Cardiology Working Group on peripheral circulation. Atherosclerosis. 2015;241(2):507–532. https://doi.org/10.1016/j.atherosclerosis.2015.05.007

13. 13 Robinson J.G., Williams K.J., Gidding S., et al. Eradicating the Burden of Atherosclerotic Cardiovascular Disease by LoweringApolipoprotein B Lipoproteins Earlier in Life. J Am Heart Assoc. 2018;7(20). https://doi.org/10.1161/jaha.118.009778

14. 14 Kamstrup P.R. Lipoprotein(a): the common, likely causal, yet elusive risk factor for cardiovascular disease. J Lipid Res. 2017;58(9):1731–1732. https://doi.org/10.1194/jlr.c079111

15. 15 Tsimikas S., Fazio S., Ferdinand K.C., et al. NHLBI Working Group Recommendations to Reduce Lipoprotein(a)-Mediated Risk of Cardiovascular Disease and Aortic Stenosis. J Am CollCardiol. 2018;71(2):177-192. https://doi.org/10.1016/j.jacc.2017.11.014

16. 16 Mozaffarian D., Lemaitre R.N., King I.B., et al. Plasma Phospholipid Long-Chain ω-3 Fatty Acids and Total and Cause-Specific Mortality in Older Adults. Ann Intern Med. 2013;158(7):515–525. https://doi.org/10.7326/0003-4819-158-7-201304020-00003

17. 17 Eckel R.H., Jakicic J.M., Ard J.D., et al. 2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk. Circulation. 2013;129(25 suppl 2):S76-S99. https://doi.org/10.1161/01.cir.0000437740.48606.d1

18. 18 de Lorgeril M., Salen P., Martin J.-L., et al. Mediterranean Diet, Traditional Risk Factors, and the Rate of Cardiovascular Complications After Myocardial Infarction. Circulation. 1999;99(6):779–785. https://doi.org/10.1161/01.cir.99.6.779

19. 19 Estruch R., Ros E., Salas-Salvado J., et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with ExtraVirgin Olive Oil or Nuts. N Engl J Med. 2018;378(25):e34. https://doi.org/10.1056/NEJMoa1800389

20. 20 Lu Z., Kou W., Du B., et al. Effect of Xuezhikang, an Extract From Red Yeast Chinese Rice, on Coronary Events in a Chinese Population With Previous Myocardial Infarction. Am J Cardiol. 2008;101(12):1689–1693. https://doi.org/10.1016/j.amjcard.2008.02.056

21. 21 Li Y., Jiang L., Jia Z., et al. A Meta-Analysis of Red Yeast Rice: An Effective and Relatively Safe Alternative Approach for Dyslipidemia. PLoS One. 2014;9(6):e98611. https://doi.org/10.1371/journal.pone.0098611

22. 22 Bays H. Statin safety: an overview and assessment of the data. Am J Cardiol. 2006;97:6-26.

23. 23 Deedwania P., Stone P.H., BaireyMerz C.N., et al. Effects of Intensive Versus Moderate LipidLowering Therapy on Myocardial Ischemia in Older Patients With Coronary Heart Disease. Circulation. 2007;115(6):700-707. https://doi.org/10.1161/circulationaha.106.654756

24. 24 Abifadel M., Varret M., Rabès J.-P., et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34(2):154156. https://doi.org/10.1038/ng1161

25. 25 Norata G.D., Tibolla G., Catapano A.L. Targeting PCSK9 for Hypercholesterolemia. Annual Review of Pharmacology and Toxicology. 2014;54(1):273-293. https://doi.org/10.1146/annurev-pharmtox011613-140025

26. 26 Kukharchuk V.V., Bazhan S.S. Proprotein convertase subtilisinkexin type 9 (PCSK9) – regulator of expression of low-density lipoprotein receptors. Atherosclerosis and dyslipidemia. 2013;2:19-26. (In Russ.)

27. 27 Greig S.L., Deeks E.D. Alirocumab: a review in hypercholesterolemia. Am J Cardiovasc Drugs. 2016;16(2):141-152.

28. 28 Sorokin E.V., Karpov Yu.A. Alirocumab - a representative of a new class of lipid-lowering drugs. Atmosphere. Cardiology News. 2016;3. (In Russ.) URL: https://cyberleninka.ru/article/n/alirokumab-predstavitel-novogo-klassa-gipolipidemicheskih-preparatov

29. 29 Karpov Yu.A., Talitsky K.A. Evolocumab – a representative of a new class of lipid-lowering drugs. Cardiology news. 2015;4:2128. (In Russ.)

30. 30 Kukharchuk V.V., Bazhan S.S. Proprotein convertase subtilisinkexin type 9 (PCSK9) – regulator of expression of low-density lipoprotein receptors. Atherosclerosis and dyslipidemia. 2013;2:19-26. (In Russ.)

31. 31 Korneva V.A., Kuznetsova T.Yu., Vezikova N.N. Experience of using evolocumab therapy in patients with familial hypercholesterolemia (in Karelia). Eurasian Journal of Cardiology. 2020;2:42-47. (In Russ.)

32. 32 Kukharchuk V.V., Yezhov M.V., Sergienko I.V., et al. Diagnostics and correction of lipid metabolism disorders for the prevention and treatment of atherosclerosis. Russian guidelines, VII revision. Atherosclerosis and dyslipidemia. 2020;1:7-40. (In Russ.)

33. 33 Shimada Y J., Cannon C.P. PCSK9 (Proproteinconvertase sub-tilisin/kexin type 9) inhibitors: past, present, and the future. Eur. Heart J. 2015;36(36):2415-2424.

34. 34 Kastelein J.J., Robinson J.G., Farnier M., Krempf M., Langslet G., Lorenzato C., Gipe D.A., Baccara-Dinet M.T. Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy: design and rationale of the ODYSSEY FH studies. Cardiovasc Drugs Ther 2014; 28(3): 281–289.

35. 35 Navarese E.P., Kolodziejczak M., Kereiakes D.J., Tantry U.S., O’Connor C., Gurbel P.A. Proprotein convertase subtilisin/kexin type 9 antibodies for acute coronary syndrome: a narrative review. AnnInternMed. 2016;164(9): 600–607.

36. 36 Kühnast S., van der Hoorn J.W., Pieterman E.J., van den Hoek A.M., Sasiela W.J., Gusarova V., Peyman A., Schäfer H.L., Schwahn U., Jukema J.W., Princen H.M. Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances the effect of a statin. J Lipid Res. 2014;55(10):2103–2112.

37. 37 Goldberg A.C., Hopkins P.N., Toth P.P., Ballantyne C.M., Rader D.J., Robinson J.G. et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J. Clin. Lipidol. 2011;5(3Suppl.): S1—8.

38. 38 Kukharchuk V.V., Malyshev P.P., Meshkov A.N. Familial hypercholesterolemia: modern aspects of diagnostics, prevention and therapy. Cardiology. 2009;(1):76–83. (In Russ.)

39. 39 Luirink I.K., Hutten B.A., Wiegman A. Optimizing Treatment of Familial Hypercholesterolemia in Children and Adolescents. Curr.Cardiol. Rep. 2015;17(9):629.

40. 40 Daniels S.R. Familial Hypercholesterolemia: The Reason to Screen Children for Cholesterol Abnormalities. J. Pediatr. 2016;170:7-8.

41. 41 The Demographic Yearbook of Russia. Federal State Statistics Service of Russia (Rosstat). 2014. (In Russ.)