The effectiveness of ω-3 polyunsaturated fatty acids combined therapy in the correction of dyslipidemia

• Elena K. Serezhina
• Andrey G. Obrezan

Abstract

Due to the achievements of pharmacological therapy the strict control of the low and very low density lipoprotein’s levels is achieved. However, atherosclerosis-associated cardiovascular diseases still remain one of the leading non-infectious cardiovascular pathologies. Currently, hypertriglyceridemia is considered as the new residual risk factor. However, the results of studies that focused on the correction of this condition with the help of ω‑3 polyunsaturated fatty acid preparations remain contradictory.

The aim of our study is to evaluate the effectiveness of the administration of ω‑3 polyunsaturated fatty acids with highly purified pharmaceutical eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in patients with hypertriglyceridemia.

Material and methods. 241 patients have participated in this randomized clinical trial. Participants in an equal ratio of 1:1:1 were divided into 3 groups depending on the dosage of ω‑3 polyunsaturated fatty acids: EPA 4 g/day in combination with DHA, EPA 2 g/day in combination with DHA and the control group. The lipidogram parameters were evaluated before the start of the study and 6 months after the start of taking the drugs. Participants were required to stop taking fish oil or other foods rich in ω‑3 fatty acids, and any herbal or dietary supplements that may regulate lipid levels. If the patient had already taken pharmacological lipid-lowering therapy, it was maintained without correction throughout the study.

Results. Daily intake of 4 g of EPA in combination with DHA, regardless of concomitant combination therapy, is associated with a decrease in total cholesterol by -6.46%, and VLDL cholesterol by -18.68%, TG by -25.77% compared with baseline, and when compared with the control group – by 23.71%. The difference in the change in TG levels between EPA at a dose of 2 g/day was not statistically significant. The administration of this group of drugs in any of the dosages and combinations did not lead to a significant increase in LDL levels compared with the basic therapy prescribed before the study.

Conclusion. Combined ω‑3 polyunsaturated fatty acids with highly purified pharmaceutical eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at a dosage of 4 g/day, both in combination with statins and without their background, reduce the level of triglycerides, VLDL and total cholesterol without significantly increasing LDL in serum in patients with hypertriglyceridemia.

Keywords:hypertriglyceridemia; ω 3 polyunsaturated fatty acids; eicosapentaenoic acid; docosahexaenoic acid; atherosclerosis-associated cardiovascular diseases

References

1. Lavie C.J. Cardiovascular statistics. Prog Cardiovasc Dis. 2023; 79: 112–3. DOI: https://doi.org/10.1016/j.pcad.2023.07.005

2. Fan J., Watanabe T. Atherosclerosis: known and unknown. Pathol Int. 2022; 72 (3):151–60. DOI: https://doi.org/10.1111/pin.13202

3. Schwartz G.G., Steg P.G., Szarek M., Bhatt D.L., Bittner V.A., Diaz R., Edelberg J.M., Goodman S.G., Hanotin C., Harrington R.A., Wouter Jukema J., Lecorps G., Mahaffey K.W., Moryusef A., Pordy R., Quintero K., Roe M.T., Sasiela W.J., Tamby J.-F., Tricoci P., White H.D., Zeiher A.M.; ODYSSEY OUTCOMES committees and investigators. Alirocumab. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018; 379: 2097–107.

4. Rosinger A., Carroll M.D., Lacher D., Ogden C. Trends in total cholesterol, triglycerides, and low-density lipoprotein in US adults, 1999–2014. JAMA cardiology. 2017; 2 (3): 339–41.

5. Silverman M.G., Ference B.A., Im K., Wiviott S.D., Giugliano R.P., Grundy S.M., Braunwald E., Sabatine M.S. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA. 2016; 316: 1289–97.

6. Laufs U., Parhofer K.G., Ginsberg H.N., Hegele R.A. Clinical review on triglycerides. Eur Heart J. 2020; 41: 99–109c. DOI: https://doi.org/10.1093/eurheartj/ehz785

7. Marx N., Federici M., Schütt K.; ESC Scientific Document Group. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes: Developed by the task force on the management of cardiovascular disease in patients with diabetes of the European Society of Cardiology (ESC). European Heart Journal. 2023; 44 (39): 4043–140. DOI: https://doi.org/10.1093/eurheartj/ehad192

8. Bhatt D.L, Steg P.G., Miller M., Brinton E.A., Jacobson T.A., Ketchum S.B., Doyle Jr R.T., Juliano R.A., Jiao L., Granowitz C., Tardif J.-C., Ballantyne C.M.; REDUCE-IT investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019; 380: 11–22.

9. Bhatt D.L., Steg P.G., Miller M., Brinton E.A., Jacobson T.A., Ketchum S.B., Doyle Jr R.T., Juliano R.A., Jiao L., Granowitz C., Tardif J.-C., Gregson J., Pocock S.J., Ballantyne C.M.; REDUCE-IT investigators. Effects of icosapent ethyl on total ischemic events: from REDUCE-IT. J Am Coll Cardiol. 2019; 73: 2791–802.

10. Kobalava Zh.D., Konradi A.O., Nedogoda S.V., Shlyakhto E.V., Arutyunov G.P., Baranova E.I., Barbarash O.L., Boitsov S.A., Vavilova T.V., Villevalde S.V., Galyavich A.S., Glezer M.G., Grineva E.N., Grinstein Yu.I., Drapkina O.M., Zhernakova Yu.V., Zvartau N.E., Kislyak O.A., Koziolova N.A., Kosmacheva E.D., Kotovskaya Yu.V., Libis R.A., Lopatin Yu.M., Nebiridze D.V., Nedoshivin A.O., Ostroumova O.D., Oschepkova E.V., Ratova L.G., Skibitsky V.V., Tkacheva O.N., Chazova I.E., Chesnikova A.I., Chumakova G.A., Shalnova S.A., Shestakova M.V., Yakushin S.S., Yanishevsky S.N. Arterial hypertension in adults. Clinical guidelines 2020. Rossiysliy kardiologicheskiy zhurnal [Russian Journal of Cardiology]. 2020; 25 (3): 3786. DOI: https://doi.org/10.15829/1560-4071-2020-3-3786 (in Russian)

11. Chernyavsky M.A., Irtyuga O.B., Yanishevsky S.N., Alieva A.S., Samochernykh K.A., Abramov K.B., Vavilova T.V., Lukyanchikov V.A., Kurapeev D.I., Vanyurkin A.G., Chernova D.V., Shelukhanov N.K., Kozlyonok А.V., Kavteladze Z.A., Malevanny M.V., Vinogradov R.A., Khafizov T.N., Ivanova G.E., Zhukovskaya N.V., Fokin A.A., Ignatiev I.M., Karpenko A.A., Ignatenko P.V., Astapov D.A., Semenov V. Yu., Porkhanov V.A., Krylov V.V., Usachev D. Yu., Svetlikov A.V., Alekyan B.G., Akchurin R.S., Chernyavsky A.M., Konradi A.O., Shlyakhto E.V. Russian consensus statement on the diagnosis and treatment of patients with carotid stenosis. Rossiysliy kardiologicheskiy zhurnal [Russian Journal of Cardiology]. 2022; 27 (11): 5284. DOI: https://doi.org/10.15829/1560-4071-2022-5284 (in Russian)

12. Xue S., Su Z., Liu D. Immunometabolism and immune response regulate macrophage function in atherosclerosis. Ageing Res Rev. 2023; 90: 101993. DOI: https://doi.org/10.1016/j.arr.2023.101993

13. Bu L.L., Yuan H.H., Xie L.L., Guo M.H., Liao D.-F., Zheng X.-L. New dawn for atherosclerosis: vascular endothelial cell senescence and death. Int J Mol Sci. 2023; 24 (20): 15160. DOI: https://doi.org/10.3390/ijms242015160

14. Yokoyama M., Origasa H., Matsuzaki M., Matsuzawa Y., Investigators JElisJ: Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007; 369: 1090–8.

15. Nicholls S.J., Lincoff A.M., Garcia M., Bash D., Ballantyne C.M., Barter P.J., Davidson M.H., Kastelein J.J.P., Koenig W., McGuire D.K., Mozaffarian D., Ridker P.M., Ray K.K., Katona B.G., Himmelmann A., Loss L.E., Rensfeldt M., Lundström T., Agrawal R., Menon V., Wolski K., Nissen S.E. Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk: the STRENGTH randomized clinical trial. JAMA. 2020; 324: 2268–80.

16. Bays H.E., Ballantyne C.M., Kastelein J.J., Isaacsohn J.L., Braeckman R.A., Soni P.N. Eicosapentaenoic acid ethyl ester (AMR 101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] trial). Am J Cardiol. 2011; 108: 682–90.

17. Mozaffarian D., Maki K.C., Bays H.E.; TRILOGY (Study of CaPre in Lowering Very High Triglycerides) investigators. Effectiveness of a Novel ω-3 Krill Oil Agent in Patients With Severe Hypertriglyceridemia: A Randomized Clinical Trial. JAMA Netw Open. 2022; 5 (1): e2141898.

18. Sezai A., Unosawa S., Taoka M., Osaka S., Obata K., Kanno S., Sekino H., Tanaka M. Long-term comparison of ethyl icosapentate vs. Omega-3-Acid ethyl in patients with cardiovascular disease and hypertriglyceridemia (DEFAT trial). Circulation Journal. 2019; 83 (6): 1368–76.

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)