Effect of the Combination of Atorvastatin and Ethylmethylhydroxypyridine Malate on the Lipid Profile in Patients with Coronary Heart Disease
Objective:to determine the nature of the effect of combining atorvastatin with the antioxidant drug ethylmethylhydroxypyridine malate on the lipid profile of patients with coronary heart disease. A pilot randomized clinical trial of 60 patients with coronary artery disease was carried out. The patients were divided into two equal groups. The first group (n = 30) consisted of patients who received basic therapy for coronary artery disease (antiplatelet agents, statins, beta-blockers, antianginal drugs) with a dosage of atorvastatin 20 mg/day. In the second one (n = 30), in addition to the basic drugs with 20 mg/day of atorvastatin, patients received ethylmethylhydroxypyridine malate in tablet form at a dose of 300 mg per day. The patients were comprehensively examined with an assessment of the lipid profile in the blood. With initial hypercholesterolemia in the first group of patients after 60 days of treatment, the level of total cholesterol decreased by 25 % from 6,63 ± 0,33 to 4,95 ± 0,45 mmol/l (p < 0,01), the level of low density lipoprotein cholesterol (LDL cholesterol) decreased by 32 % from 4,31 ± 0,32 to 2,91 ±0,45 (p < 0,05), and the atherogenic coefficient (Сa) decreased by 32 % from 5,06 ± 0,67 to 3,43 ± 0,63 (p > 0,05). In the second group, the level of total cholesterol decreased by 34 % from 6,98 ± 0,50 to 4,58 ± 0,47 mmol/l (p < 0,01), the level of LDL cholesterol decreased by 47 % from 4,53 ± 0,48 to 2,39 ± 0,54 (p < 0,01) and Сa decreased by 47 % from 4,59 ± 0,55 to 2,44 ± 0,39 (p < 0,01). With initially normal values of serum cholesterol (up to 5,0 mmol/l). No significant difference between the comparison groups in the dynamics of treatment was revealed. The synergistic effect of the combination of atorvastatin and the antioxidant drug ethylmethylhydroxypyridine malate on the lipid profile of patients with coronary heart disease has been proven.
Romashchenko O.V., Khokhlov A.L., Alferov P.K., Yakunchenko T.I., Pyatakovich F.A., Mevsha O.V. 2024. Effect of the Combination of Atorvastatin and Ethylmethylhydroxypyridine Malate on the Lipid Profile in Patients with Coronary Heart Disease. Challenges in Modern Medicine, 47(4): 449–464 (in Russian). DOI: 10.52575/2687-0940-2024-47-4-449-464
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Barbarash O.L., Karpov Yu.A., Kashtalap V.V., Boschenko A.A., Ruda M.M., Akchurin R.S., Alekyan B.G., Aronov D.M., Belenkov Yu.N., Boytsov S.A., Boldueva S.A., Bubnova M.G., Vasyuk Yu.A., Gabinsky Ya.L., Galyavich A.S., Glezer M.G., Golubev E.P., Golukhova E.Z., Grinshtein Yu.I., Davidovich I.M., Ezhov M.V., Karpov R.S., Korennova O.Yu., Kosmacheva E.D., Koshelskaya O.A., Kukharchuk V.V., Lopatin Yu.M., Mironov V.M., Martsevich S.Yu., Mirolyubova O.A., Mikhin V.P., Nedoshivin A.O., Oleinikov V.E., Panov A.V., Panchenko E.P., Perepech N.B., Petrova M.M., Pozdnyakov Yu.M., Protasov K.V., Savenkov M.P., Samko A.N., Skibitsky V.V., Soboleva G.N., Shalaev S.V., Shaposhnik I.I., Shevchenko A.O., Shevchenko O.P., Shiryaev A.A., Shlyakhto E.V., Chumakova G.A., Yakushin S.S. 2020. Clinical Practice Guidelines for Stable coronary artery disease 2020. Russian Journal of Cardiology; 25(11): 4076 (in Russian) doi:10.15829/1560-4071- 2020-4076
Ezhov M.V., Kukharchuk V.V., Sergienko I.V., Alieva A.S., Antsiferov M.B., Ansheles A. A., Arabidze G.G., Aronov D.M., Arutyunov G.P., Akhmedzhanov N.M., Balakhonova T.V., Barbarash O.L., Boytsov S.A., Bubnova M.G., Voevoda M.I., Galstyan G.R., Galyavich A.S., Gornyakova N.B., Gurevich V.S., Dedov I.I., Drapkina O.M., Duplyakov D.V., Eregin S.Ya., Ershova A.I., Irtyuga O.B., Karpov R.S., Karpov Yu. A., Kachkovsky M.A., Kobalava Zh.D., Koziolova N.A., Konovalov G.A., Konstantinov V.O., Kosmacheva E.D., Kotovskaya Yu.V., Martynov A.I., Meshkov A.N., Nebieridze D.V., Nedogoda S.V., Obrezan A.G., Oleinikov V.E., Pokrovsky S.N., Ragino Yu.I., Rotar O.P., Skibitsky V.V., Smolenskaya O.G., Sokolov A.A., Sumarokov A.B., Tkacheva O.N., Filippov A.E., Halimov Yu.Sh., Chazova I.E., Shaposhnik I.I., Shestakova M.V., Yakushin S.S., Shlyakhto E.V. 2023. Narusheniya lipidnogo obmena. Klinicheskiye rekomendatsii 2023 [Disorders of lipid metabolism. Clinical Guidelines 2023.] Russian Journal of Cardiology. 28(5):5471. doi:10.15829/1560-4071-2023-5471. (In Russian)
Kukes V.G., Goroshko O.A. 2014. Vozmozhnosti vliyaniya na biosintez i metabolizm kholesterina i lipoproteinov v organizme cheloveka [Possibilities of Influence on Biosynthesis and Metabolism of Cholesterol and Lipoproteins in the Human Body]. Medicines and Rational Pharmacotherapy. 1: 8–12.
Kukharchuk V.V., Ezhov M.V., Sergienko I.V., Arabidze G.G., Bubnova M.G., Balakhonova T.V., Gurevich V.S., Kachkovsky M.A., Konovalov G.A., Konstantinov V.O., Malyshev P.P., Pokrovsky S.N., Sokolov A.A., Sumarokov A.B., Gornyakova N.B., Obrezan A.G., Shaposhnik I.I. 2020. Diagnostika i korrektsiya narusheniy lipidnogo obmena s tsel'yu profilaktiki i lecheniya ateroskleroza. Rossiyskiye rekomendatsii, VII peresmotr [Diagnostics and Correction of Lipid Metabolism Disorders for the Prevention and Treatment of Atherosclerosis. Russian Guidelines, VII Revision]. Atherosclerosis and Dyslipidemia; 1: 7–40. doi: 10.34687/2219-8202.JAD.2020.01.0002
Usacheva E.V., Nelidova A.V., Kulikova O.M., Flyanku I.P. 2021. Smertnost' trudosposobnogo naseleniya Rossii ot serdechno-sosudistykh zabolevaniy [Mortality of Russian Able-Bodied Population from Cardiovascular Diseases in 2016] Gigiena i Sanitariya (Hygiene and Sanitation, Russian Journal). 100(2): 159–165. doi:10.47470/0016-9900-2021-100-2-159-165
Sharapova O.V., Kicha D.I., Gerasimova L.I., Rukodaynyy O.V., Fomina R.V., Evzerikhina A.V., Barsukova E.V. 2022. Kartograficheskiy analiz pokazateley zabolevayemosti i smertnosti ot bolezney sistemy krovoobrashcheniya naseleniya Rossiyskoy Federatsii [Map Analysis of Morbidity and Mortality from Blood Circulatory System Diseases of the Population of the Russian Federation (2010–2019)]. Complex Issues of Cardiovascular Diseases. 11(1): 56–68. doi: 10.17802/2306-1278-2022-11-1-56-68
Abdul-Rahman T., Bukhari S.M., Herrera E.C., Awuah W.A., Lawrence J., de Andrade H., Patel N., Shah R., Shaikh R., Capriles C.A., Ulusan S. 2022. Lipid Lowering Therapy: An Era Beyond Statins. Current Problems in Cardiology. 47(12): 101342. doi: 10.1016/j.cpcardiol.2022.101342.
Boudoulas K.D., Triposciadis F., Geleris P., Boudoulas H. 2016. Coronary Atherosclerosis: Pathophysiologic Basis for Diagnosis and Management. Prog Cardiovasc Dis. 58(6): 676–92. doi: 10.1016/j.pcad.2016.04.003.
Fang W., Xie S., Deng W. 2024. Ferroptosis Mechanisms and Regulations in Cardiovascular Diseases in the Past, Present, and Future. Cell. Biol. Toxicol. 40(1): 17. doi: 10.1007/s10565-024-09853-w.
Ference B.A., Graham I., Tokgozoglu L., Catapano A.L. 2018. Reprint of: Impact of Lipids on Cardiovascular Health: JACC Health Promotion Series. J. Am. Coll. Cardiol. 72(23 Pt B): 2980–2995. doi: 10.1016/j.jacc.2018.10.021.
Gaschler M.M., Stockwell B.R.. 2017. Lipid Peroxidation in Cell Death. Biochem Biophys Res Commun. 482(3): 419–425. doi: 10.1016/j.bbrc.2016.10.086.
Gasparovic I., Artemiou P., Domonkos A., Bezak B., Gazova A., Kyselovic J., Hulman M. 2023. Multivessel Coronary Disease and Severe Atherosclerotic Aorta: Real-World Experience. Medicina (Kaunas). 59(11): 1943. doi: 10.3390/medicina59111943.
Grundy S.M., Stone N.J., Bailey A.L., Beam C., Birtcher K.K., Blumenthal R.S., Braun L.T., de Ferranti S., Faiella-Tommasino J., Forman D.E., Goldberg R., Heidenreich P.A., Hlatky M.A., Jones D.W., Lloyd-Jones D., Lopez-Pajares N., Ndumele C.E., Orringer C.E., Peralta C.A., Saseen J.J., Smith S.C. Jr, Sperling L., Virani S.S., Yeboah J. 2019. 2018. AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J. Am. Coll Cardiol. 73(24): 3168–3209. doi: 10.1016/j.jacc.2018.11.002.
Hadzi-Petrushev N., Dimovska K., Jankulovski N., Mitrov D., Mladenov M. 2018. Supplementation with Alpha-Tocopherol and Ascorbic Acid to Nonalcoholic Fatty Liver Disease’s Statin Therapy in Men. Advances in Pharmacological Sciences. 2018: 4673061. doi: 10.1155/2018/4673061.
Knuuti J., Wijns W., Saraste A., Capodanno D., Barbato E., Funck-Brentano C., Prescott E., Storey R.F., Deaton C., Cuisset T., Agewall S., Dickstein K., Edvardsen T., Escaned J., Gersh B.J., Svitil P., Gilard M., Hasdai D., Hatala R., Mahfoud F., Masip J., Muneretto C., Valgimigli M., Achenbach S., Bax J.J.; ESC Scientific Document Group. 2020. 2019 ESC Guidelines for the Diagnosis and Management of Chronic Coronary Syndromes. Eur. Heart. J. 41(3): 407–477. doi: 10.1093/eurheartj/ehz425.
Mach F., Baigent C., Catapano A.L., Koskinas K.C., Casula M., Badimon L., Chapman M.J., De Backer G.G., Delgado V., Ference B.A., Graham I.M., Halliday A., Landmesser U., Mihaylova B., Pedersen T.R., Riccardi G., Richter D.J., Sabatine M.S., Taskinen M.R., Tokgozoglu L., Wiklund O.; ESC Scientific Document Group. 2020. 2019 ESC/EAS Guidelines for the Management of Dyslipidaemias: Lipid Modification to Reduce Cardiovascular Risk. Eur. Heart. J. 41(1): 111–188. doi: 10.1093/eurheartj/ehz455.
Mach F., Ray K.K., Wiklund O., Corsini A., Catapano A.L., Bruckert E., De Backer G., Hegele R.A., Hovingh G.K., Jacobson T.A., Krauss R.M., Laufs U., Leiter L.A., März W., Nordestgaard B.G., Raal F.J., Roden M., Santos R.D., Stein E.A., Stroes E.S., Thompson P.D., Tokgözoglu L., Vladutiu G.D., Gencer B., Stock J.K., Ginsberg H.N., Chapman M.J.; European Atherosclerosis Society Consensus Panel. 2018. Adverse Effects of Statin Therapy: Perception vs. the Evidence – Focus on Glucose Homeostasis, Cognitive, Renal and Hepatic Function, Haemorrhagic Stroke and Cataract. Eur. Heart. J. 39(27): 2526–2539. doi: 10.1093/eurheartj/ehy182.
Masana L., Plana N., Andreychuk N., Ibarretxe D. 2023. Lipid Lowering Combination Therapy: From Prevention to Atherosclerosis Plaque Treatment. Pharmacological Research. 190: 106738. doi: 10.1016/j.phrs.2023.106738
Mizrahi M., Adar T., Lalazar G., Nachman D., El Haj M., Ben Ya'acov A., Lichtenstein Y., Shabat Y., Kanovich D., Zolotarov L., Ilan Y. 2018. Glycosphingolipids Prevent APAP and HMG-CoA Reductase Inhibitors-mediated Liver Damage: A Novel Method for "Safer Drug" Formulation that Prevents Drug-induced Liver Injury. J. Clin. Transl. Hepatol. 6(2): 127–134. doi: 10.14218/JCTH.2017.00071.
Newman C.B. 2022. Safety of Statins and Nonstatins for Treatment of Dyslipidemia. Endocrinol Metab Clin North Am. 51(3): 655–679. doi: 10.1016/j.ecl.2022.01.004.
Punetha M., Saini S., Chaudhary S., Bala R., Sharma M., Kumar P., Kumar D., Yadav P.S. 2023. Mitochondria-Targeted Antioxidant MitoQ Ameliorates ROS Production and Improves Cell Viability in Cryopreserved Buffalo Fibroblasts. Tissue Cell. 82: 102067. doi: 10.1016/j.tice.2023.102067.
Ralapanawa U., Sivakanesan R. 2021. Epidemiology and the Magnitude of Coronary Artery Disease and Acute Coronary Syndrome: A Narrative Review. J. Epidemiol. Glob. Health. 11(2): 169–177. doi: 10.2991/jegh.k.201217.001.
Ray K.K., Reeskamp L.F., Laufs U., Banach M., Mach F., Tokgözoğlu L.S., Connolly D.L., Gerrits A.J., Stroes E.S.G., Masana L., Kastelein J.J.P. 2022. Combination Lipid-Lowering Therapy as First-Line Strategy in Very High-Risk Patients. Eur. Heart. J. 43(8): 830–833. doi: 10.1093/eurheartj/ehab718.
Rejraji H.P., Brugnon F., Sion B., Maqdasy S., Gouby G., Pereira B., Marceau G., Gremeau A.-S., Drevet J., Grizard G., Janny L., Tauveron I., Rejraji P. 2014. Evaluation of Atorvastatin Efficacy and Toxicity on Spermatozoa, Accessory Glands and Gonadal Hormones of Healthy Men: A Pilot Prospective Clinical Trial. Reproductive Biology and Endocrinology. 12: 65. doi: 10.1186/1477-7827-12-65.
Renman D., Lundberg E., Gunnarsson U., Strigård K. 2017. Statin Consumption as a Risk Factor for Developing Colorectal Cancer: A Retrospective Case Study. World Journal of Surgical Oncology. 15(1): 222. doi: 10.1186/s12957-017-1287-0.
Ridker P.M., Bhatt D.L., Pradhan A.D., Glynn R.J., MacFadyen J.G., Nissen S.E. 2023. PROMINENT, REDUCE-IT, and STRENGTH Investigators. Inflammation and cholesterol as Predictors of Cardiovascular Events Among Patients Receiving Statin Therapy: A Collaborative Analysis of Three Randomised Trials. Lancet. 401(10384): 1293-1301. doi: 10.1016/S0140-6736(23)00215-5.
Romaschenko O.V., Gorbach T.V., Alferov P.K., Grischenko N.D., Pokrovskaya T.G., Rumbesht V.V. 2020. Endothelioprotective Effect of a Combination of Statin with Antioxidant in the Treatment of Patients with Coronary Heart Disease. Journal of critical reviews. 7(10): 571–575. doi: 10.31838/jcr.07.10.113.
Romaschenko O.V., Pokrovsky M.V., Nadezhdin S.V., Gorbach T.V., Alferov P.K., Grischenko N.D., Rumbesht V.V. 2022. Personalized Approaches to the Use of the Antioxidant Ethoxidol in Patients with Coronary Heart Disease. J. Nanostruct. 12(2): 343–352. doi: 10.22052/JNS.2022.02.011
Shivakumar A., Yogendra Kumar M.S. 2018. Critical Review on the Analytical Mechanistic Steps in the Evaluation of Antioxidant Activity. Crit. Rev. Anal. Chem. 48(3): 214–236. doi: 10.1080/10408347.2017.1400423.
Sokalska A., Stanley S.D., Villanueva J.A., Ortega I., Duleba A.J. 2014. Comparison of Effects of Different Statins on Growth and Steroidogenesis of Rat Ovarian Theca-Interstitial Cells. Biology of reproduction. 90(2): 44. doi: 10.1095/biolreprod.113.114843.
Virani S.S., Newby L.K., Arnold S.V., Bittner V., Brewer L.C., Demeter S.H., Dixon D.L., Fearon W.F., Hess B., Johnson H.M., Kazi D.S., Kolte D., Kumbhani D.J., LoFaso J., Mahtta D., Mark D.B., Minissian M., Navar A.M., Patel A.R., Piano M.R., Rodriguez F., Talbot A.W., Taqueti V.R., Thomas R.J., van Diepen S., Wiggins B., Williams M.S.; Peer Review Committee Members. 2023. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 148(9): e9-e119. doi: 10.1161/CIR.0000000000001168.
Visseren F.L.J., Mach F., Smulders Y.M., Carballo D., Koskinas K.C., Bäck M., Benetos A., Biffi A., Boavida J.M., Capodanno D., Cosyns B., Crawford C., Davos C.H., Desormais I., Di Angelantonio E., Franco O.H., Halvorsen S., Hobbs F.D.R., Hollander M., Jankowska E.A., Michal M., Sacco S., Sattar N., Tokgozoglu L., Tonstad S., Tsioufis K.P., van Dis I., van Gelder I.C., Wanner C., Williams B.; ESC National Cardiac Societies; ESC Scientific Document Group. 2021. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur. Heart. J. 42(34): 3227–3337. doi: 10.1093/eurheartj/ehab484.
Wu M.Y., Li C.J., Hou M.F., Chu P.Y. 2017. New Insights into the Role of Inflammation in the Pathogenesis of Atherosclerosis. Int. J. Mol. Sci. 18(10): 2034. doi: 10.3390/ijms18102034.
Xu X., Xu X.D., Ma M.Q., Liang Y., Cai Y.B., Zhu Z.X., Xu T., Zhu L., Ren K. 2024. The Mechanisms of Ferroptosis and its Role in Atherosclerosis. Biomed Pharmacother. 171: 116112. doi: 10.1016/j.biopha.2023.116112.
The work was carried out with the financial support of Medimex LLC (Kurgan, Russia).