Clinical and pharmacological aspects of combined lipid-lowering therapy
DOI: 10.32364/2587-6821-2025-9-9-4
A.S. Dukhanin
Pirogov Russian National Research Medical University, Moscow, Russian Federation
The use of fixed combinations (FC) of statin plus ezetimibe, compared to loose combinations (LC), improves the efficacy of pharmacological therapy for hypercholesterolemia. Real-world clinical studies indicate that, among patients receiving LC of statin and ezetimibe, the risk ratio for treatment discontinuation is higher compared to those treated with FC. Numerous studies have demonstrated a strong association between high treatment adherence and a reduced incidence of major adverse cardiovascular events (MACE). Fixed combinations are pharmaceutical formulations in which a single dose contains two or more active substances, manufactured in a definite dosage form — such as a tablet or capsule. The capsule form of FC, which contains rosuvastatin and ezetimibe as separate tablets within a single capsule, offers several benefits. These include the complete exclusion of lactose as an excipient, with its substitution by mannitol; absence of restrictions for patients with galactose intolerance, lactase deficiency, or glucose-galactose malabsorption; and the omission of film coating (tablets contained within the capsule are uncoated). The natural gelatin capsule itself serves as protection against environmental factors and masks the taste, thereby eliminating the need for a film coating.
Keywords: hypercholesterolemia, statins, rosuvastatin, ezetimibe, fixed combination, treatment persistence, medication adherence.
For citation: Dukhanin A.S. Clinical and pharmacological aspects of combined lipid-lowering therapy. Russian Medical Inquiry. 2025;9(9):554–558 (in Russ.). DOI: 10.32364/2587-6821-2025-9-9-4
About the author:
Alexander S. Dukhanin — Dr. Sc. (Med.), Professor of the Department of Molecular Pharmacology and Radiobiology named after Academician P.V. Sergeev, Pirogov Russian National Research Medical University; 1, Ostrovityanov str., Moscow, 117513, Russian Federation; ORCID iD 0000-0003-2433-7727
Contact information: Aleksander S. Dukhanin, e-mail: das03du@mail.ru
Financial Disclosure: the author has no a financial or property interest in any material or method mentioned.
There is no conflict of interest.
Received 30.06.2025.
Revised 23.07.2025.
Accepted 15.08.2025.
2. Chilbert M.R., VanDuyn D., Salah S. et al. Combination Therapy of Ezetimibe and Rosuvastatin for Dyslipidemia: Current Insights. Drug Des Devel Ther. 2022;16:2177–2186. DOI: 10.2147/DDDT.S332352
3. Phan B.A., Dayspring T.D., Toth P.P. Ezetimibe therapy: mechanism of action and clinical update. Vasc Health Risk Manag. 2012;8:415–427. DOI: 10.2147/VHRM.S33664
4. Michaeli D.T., Michaeli J.C., Albers S. et al. Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention. Am J Cardiovasc Drugs. 2023;23(5):477–495. DOI: 10.1007/s40256-023-00594-5
5. Merćep I., Vujević A., Strikić D. et al. Present and Future of Dyslipidaemia Treatment-A Review. J Clin Med. 2023;12(18):5839. DOI: 10.3390/jcm12185839
6. van Heek M., Farley C., Compton D.S. et al. Ezetimibe selectively inhibits intestinal cholesterol absorption in rodents in the presence and absence of exocrine pancreatic function. Br J Pharmacol. 2001;134(2):409–417.
7. Ray K.K., Haq I., Bilitou A. et al. Evaluation of contemporary treatment of high- and very high-risk patients for the prevention of cardiovascular events in Europe — Methodology and rationale for the multinational observational SANTORINI study. Atheroscler Plus. 2021;43:24–30. DOI: 10.1016/j.athplu.2021.08.003
8. Ray K.K., Molemans B., Schoonen W.M. et al. EU-wide cross-sectional observational study of lipid-modifying therapy use in secondary and primary care: the DA VINCI study. Eur J Prev Cardiol. 2021;28(11):1279–1289. DOI: 10.1093/eurjpc/zwaa047
9. Cannon C.P., De Lemos J.A., Rosenson R.S. et al. Use of lipid-lowering therapies over 2 years in GOULD, a registry of patients with atherosclerotic cardiovascular disease in the US. JAMA Cardiol. 2021;6(9):1060–1068. DOI: 10.1001/jamacardio.2021.1810
10. Rea F., Savare L., Corrao G., Mancia G. Adherence to lipid-lowering treatment by single-pill combination of statin and ezetimibe. Adv Ther. 2021;38(10):5270–5285. DOI: 10.1007/s12325-021-01892-7
11. Mazhar F., Hjemdahl P., Sjolander A. et al. Intensity of and adherence to lipid-lowering therapy as predictors of goal attainment and major adverse cardiovascular events in primary prevention. Am Heart J. 2024;269:118–130. DOI: 10.1016/j.ahj.2023.12.010
12. Lin C.P., Tung Y.C., Hsiao F.C. et al. Fixed-dose combination of amlodipine and atorvastatin improves clinical outcomes in patients with concomitant hypertension and dyslipidemia. J Clin Hypertens (Greenwich). 2020;22(10):1846–1853. DOI: 10.1111/jch.14016
13. Zhao B., He X., Wu J., Yan S. Adherence to statins and its impact on clinical outcomes: a retrospective population-based study in China. BMC Cardiovasc Disord. 2020;20(1):282. DOI: 10.1186/s12872-020-01566-2
14. Журавлева М.В., Фролов М.Ю., Лучинин Е.А. и др. Экономические аспекты фиксированных комбинаций гиполипидемических препаратов у больных в группах риска. Качественная клиническая практика. 2023;(2):42–52.Zhuravleva M.V., Frolov M.Yu., Luchinin Е.А. et al. Economic aspects of the fixed combinations of lipid lowering medicines in group risks patients. Good Clinical Practice. 2023;(2):42–52 (in Russ.).
15. Wei Q., Zhou J., Li H. et al. Medication adherence with fixed-dose versus free equivalent combination therapies: Systematic review and meta-analysis. Front Pharmacol. 2023;14:1156081. DOI: 10.3389/fphar.2023.1156081
16. Ferri N., Ruscica M., Santos R.D., Corsini A. Fixed Combination for the Treatment of Dyslipidaemia. Curr Atheroscler Rep. 2023;25(10):691–699. DOI: 10.1007/s11883-023-01142-x
17. Samnaliev M., Khan I., Potukuchi P. et al. Treatment adherence, persistence, and effectiveness of fixed dose combination versus free combination therapy of rosuvastatin ezetimibe as a lipid-lowering therapy. Front Cardiovasc Med. 2025;12:1461416. DOI: 10.3389/fcvm.2025.1461416
18. Alqifari S.F., Alshareef H., Tawfeek H.M. et al. Patient-centered innovations in ambulatory care: developing a fixed-dose tablet to enhance adherence for patients with chronic diseases. Drug Dev Ind Pharm. 2025;51(7):826–835. DOI: 10.1080/03639045.2025.2513407
19. Gautam C.S., Saha L. Fixed dose drug combinations (FDCs): rational or irrational: a view point. Br J Clin Pharmacol. 2008;65(5):795–796.
20. Janczura M., Sip S., Cielecka-Piontek J. The Development of Innovative Dosage Forms of the Fixed-Dose Combination of Active Pharmaceutical Ingredients. Pharmaceutics. 2022;14(4):834. DOI: 10.3390/pharmaceutics14040834
21. Wilkins C.A., Hamman H., Hamman J.H., Steenekamp J.H. Fixed-Dose Combination Formulations in Solid Oral Drug Therapy: Advantages, Limitations, and Design Features. Pharmaceutics. 2024;16(2):178. DOI: 10.3390/pharmaceutics16020178
22. Alburyhi M., Noman C., Saif A.A. et al. Rosuvastatin-excipient compatibility studies for advanced drug delivery systems development. World Journal of Pharmaceutical Research. 2024;13(13):1549–1582. DOI: 10.20959/wjpr202413-33126
23. Camilo Ferreira Pereira R.J., Silva Serra J.P. Solid oral multiple-unit immediate release compositions, methods and uses. Patents WO2021019499A1. (Electronic resource.) URL: https://patents.google.com/patent/WO2021019499A1/en (access date: 11.08.2025).
24. Mahavir S.V., Rachh P.R. Compatability study of selexipag and ezetimibe with selected excipients in formulation of bilayer tablet. International Journal of Health Sciences. 2022;6(S3):3276–3287. DOI: 10.53730/ijhs.v6nS3.6340
25. Mostafa M., Sayed O.M., Teaima M.H. et al. Factorial design, formulation, in vitro and in vivo evaluation of a multi-layer tablet containing ticagrelor and aspirin, for dual antiplatelet therapy. J Pharm Sci. 2025;114(7):103817. DOI: 10.1016/j.xphs.2025.103817
This work is licensed under a Creative Commons «Attribution» 4.0 License.
