Effectiveness of fixed-dose combination of rosuvastatin and ezetimibe in heterozygous familial hypercholesterolemia from the RENAISSANCE registry
https://doi.org/10.20996/1819-6446-2025-3205
EDN: XSPXJN
Abstract
Aim. To study the adequacy and effectiveness of lipid-lowering therapy (LLT) prescribed to patients with heterozygous familial hypercholesterolemia (HeFH), including fixed-dose combinations (FDC) of rosuvastatin with ezetimibe, as well as the frequency of achieving target low-density lipoprotein cholesterol (LDL-C) levels.
Material and methods. The clinical and demographic data of 3151 patients with HeFH at high or very high cardiovascular risk from the RENAISSANCE registry were retrospectively analysed. Among the 1612 individuals receiving LLT, 477 patients were treated with a combination of rosuvastatin at various doses and ezetimibe 10 mg daily, either as a free combination or as a FDC.
Results. The median age of the patients was 46.0 [32.0; 57.0] years. The median LDL-C level was 6.4 [5.3; 7.8] mmol/L. Although LLT was recommended to all participants, approximately half (49%, n=1539) were not receiving treatment. Among the 1612 patients on LLT, 44% (n=703) received statin monotherapy, and 43% (n=697) were treated with a combination of statins and ezetimibe. Of the 477 patients taking rosuvastatin with ezetimibe, the majority were active adults of working age (35-64 years): 335 (80%) vs 86 (20%), p <0.05. Most patients preferred taking rosuvastatin with ezetimibe in the FDC: 357 (74.8%) vs 120 (25.2%), p <0.05. Among those on FDC, a significantly higher proportion used Zenon® compared to other FDCs: 44.4% (n=212) vs 30.4% (n=145), p <0.05. A significant reduction in LDL-C was observed compared to baseline: 61% in the free combination group and 65% in the FDC group, including a 67% reduction in the Zenon® subgroup (p <0.001). The rate of achieving LDL-C targets among high/very high cardiovascular risk patients was lower in the free combination group compared to the FDC group, with the highest rates observed among Zenon® users: 5.8% (n=7), 17.9% (n=26), and 21.7% (n=46), respectively (p <0.01).
Conclusion. Among patients with НeFH, the use of a FDC of rosuvastatin and ezetimibe is associated with higher treatment adherence and a greater likelihood of achieving target LDL-С levels.
Keywords
About the Authors
I. A. AlekseevaRussian Federation
Irina A. Alekseeva
Moscow
U. V. Chubykina
Russian Federation
Uliana V. Chubykina
Moscow
M. V. Ezhov
Russian Federation
Marat V. Ezhov
Moscow
A. V. Tyurina
Russian Federation
Aleksandra V. Tyurina
Moscow
T. E. Kolmakova
Russian Federation
Tatiana E. Kolmakova
Moscow
N. A. Tmoyan
Russian Federation
Narek A. Tmoyan
Moscow
A. A. Sokolov
Russian Federation
Alexey A. Sokolov
Moscow
T. A. Rozhkova
Russian Federation
Tatiana A. Rozhkova
Moscow
N. S. Kurochkina
Russian Federation
Natalia S. Kurochkina
Moscow
I. V. Sergienko
Russian Federation
Igor V. Sergienko
Moscow
I. V. Avdeeva
Russian Federation
Irina V. Avdeeva
Penza
V. E. Oleynikov
Russian Federation
Valentin E. Oleynikov
Penza
A. S. Alieva
Russian Federation
Asiiat S. Alieva
St. Petersburg
N. G. Androsyuk
Russian Federation
Natalia G. Androsyuk
Astrakhan
M. A. Kiselevа
Russian Federation
Maria A. Kiselevа
Astrakhan
Yu. G. Grigorieva
Russian Federation
Yulia G. Grigorieva
Astrakhan
A. S. Asekritova
Russian Federation
Aleksandra S. Asekritova
Yakutsk
E. S. Kylbanova
Russian Federation
Elena S. Kylbanova
Yakutsk
A. V. Pavlova
Russian Federation
Anna V. Pavlova
Yakutsk; Kurgan
A. I. Ershova
Russian Federation
Alexandra I. Ershova
Moscow
A. N. Meshkov
Russian Federation
Aleksey N. Meshkov
Moscow
V. I. Mikhailina
Russian Federation
Viktoria I. Mikhailina
Moscow
A. V. Blokhina
Russian Federation
Anastasia V. Blokhina
Moscow
A. S. Limonova
Russian Federation
Alena S. Limonova
Moscow
O. V. Kopylova
Russian Federation
Oksana V. Kopylova
Moscow
A. S. Vorobyev
Russian Federation
Anton S. Vorobyev
Surgut
I. D. Astrakhantseva
Russian Federation
Irina D. Astrakhantseva
Surgut
Yu. A. Vorobyeva
Russian Federation
Yulia A. Vorobyeva
Barnaul
Yu. A. Ermakova
Russian Federation
Yulia A. Ermakova
Barnaul
D. I. Sadykova
Russian Federation
Dinara I. Sadykova
Kazan
E. S. Slastnikova
Russian Federation
Evgeniia S. Slastnikova
Kazan
L. F. Galimovа
Russian Federation
Lily F. Galimovа
Kazan
I. I. Shaposhnik
Russian Federation
Igor I. Shaposhnik
Chelyabinsk
V. V. Genkel
Russian Federation
Vadim V. Genkel
Chelyabinsk
A. V. Egorova
Russian Federation
Antonina V. Egorova
Samara
N. V. Mukha
Russian Federation
Natalia V. Mukha
Chita
P. V. Vasilenko
Russian Federation
Pavel V. Vasilenko
Chita
D. N. Zaitsev
Russian Federation
Dmitry N. Zaitsev
Irkutsk
Z. F. Kim
Russian Federation
Zulfiya F. Kim
Kazan
V. K. Zafiraki
Russian Federation
Vitaliy K. Zafiraki
Krasnodar
M. V. Zykov
Russian Federation
Mikhail V. Zykov
Sochi
V. A. Korneva
Russian Federation
Viktoria A. Korneva
Petrozavodsk
T. Yu. Kuznetsova
Russian Federation
Tatiana Yu. Kuznetsova
Petrozavodsk
Yu. A. Malyshenko
Russian Federation
Yulia A. Malyshenko
Kaliningrad
T. I. Petelina
Russian Federation
Tatiana I. Petelina
Tomsk
E. V. Mikova
Russian Federation
Ekaterina V. Mikova
Tomsk
A. M. Namitokov
Russian Federation
Alim M. Namitokov
Krasnodar
E. D. Kosmacheva
Russian Federation
Elena D. Kosmacheva
Krasnodar
I. I. Pshenichnikova
Russian Federation
Irina I. Pshenichnikova
Moscow
V. O. Konstantinov
Russian Federation
Vladimir O. Konstantinov
Saint Petersburg
S. E. Bednova
Russian Federation
Svetlana E. Bednova
Saint Petersburg
M. I. Voevoda
Russian Federation
Mikhail I. Voevoda
Novosibirsk
O. V. Timoshenko
Russian Federation
Olga V. Timoshenko
Novosibirsk
Yu. I. Ragino
Russian Federation
Yulia I. Ragino
Novosibirsk
A. E. Filippov
Russian Federation
Alexandr E. Filippov
Saint Petersburg
A. M. Tuktarov
Russian Federation
Artur M. Tuktarov
Saint Petersburg
V. S. Gurevich
Russian Federation
Victor S. Gurevich
Saint Petersburg
M. V. Muzalevskaya
Russian Federation
Maria V. Muzalevskaya
Saint Petersburg
S. A. Urazgildeevа
Russian Federation
Soreya A. Urazgildeevа
Saint Petersburg
R. A. Khokhlov
Russian Federation
Roman A. Khokhlov
Voronezh
S. V. Yarkovaya
Russian Federation
Svetlana V. Yarkovaya
Voronezh
E. A. Shutemova
Russian Federation
Elena A. Shutemova
Ivanovo
E. V. Kudelkina
Russian Federation
Ekaterina V. Kudelkina
Kurgan
N. N. Bizyaeva
Russian Federation
Natalia N. Bizyaeva
Perm
References
1. Mensah GA, Fuster V, Murray CJ, Roth GA; Global Burden of Cardiovascular Diseases and Risks Collaborators. Global burden of cardiovascular diseases and risks, 1990–2022. J Am Coll Cardiol 2023;82(25):2350-473. DOI:10.1016/j.jacc.2023.11.007.
2. Ezhov MV, Kukharchuk VV, Sergienko IV, et al. Disorders of lipid metabolism. Clinical Guidelines 2023. Russian Journal of Cardiology. 2023;28(5):5471. (In Russ.) DOI:10.15829/1560-4071-2023-5471.
3. Meshkov AN, Ershova AI, Kiseleva AV, et al. On Behalf Of The Fh-Esse-Rf Investigators. The Prevalence of Heterozygous Familial Hypercholesterolemia in Selected Regions of the Russian Federation: The FH-ESSE-RF Study. J Pers Med 2021;11(6):464. DOI:10.3390/jpm11060464.
4. Ezhov MV, Bliznyuk SA, Tmoyan NA, et al. Register of patients with familial hypercholesterolemia and patients of very high cardiovascular risk with lipid-lowering therapy underperformance (RENESSANS). Russian Journal of Cardiology. 2019;(5):7-13. (In Russ.) DOI:10.15829/1560-4071-2019-5-7-13.
5. Chubykina UV, Ezhov MV, Rozhkova TA, et al. A five-year follow-up period in homo- and heterozygous familial hypercholesterolemia patients of the RENAISSANCE registry. Ateroskleroz i dislipidemii. 2023;(1):5-18. (In Russ.) DOI:10.34687/2219-8202.JAD.2023.01.0001.
6. Chubykina UV, Ezhov MV, Rozhkova TA, et al. Compliance of patients with heterozygous familial hypercholesterolemia: 5-year follow-up of the renaissance registry. Russian Cardiology Bulletin. 2023;18(3):35-48. (In Russ.) DOI:10.17116/Cardiobulletin20231803135.
7. Cuchel M, Bruckert E, Ginsberg HN, et al.; European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35(32):2146-57. DOI:10.1093/eurheartj/ehu274.
8. Webster R, Castellano JM, Onuma OK. Putting polypills into practice: challenges and lessons learned. Lancet. 2017;389(10073):1066-74. DOI:10.1016/S0140-6736(17)30558-5.
9. Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003;326(7404):1419. DOI:10.1136/bmj.326.7404.1419.
10. Agarwal A, Mehta PM, Jacobson T, et al. Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular disease. Nat Med. 2024;30(4):1199- 209. DOI:10.1038/s41591-024-02896-w. Erratum in: Nat Med. 2024;30(8):2371. DOI: 10.1038/s41591-024-03128-x.
11. Rao S, Jamal Siddiqi T, Khan MS, et al. Association of polypill therapy with cardiovascular outcomes, mortality, and adherence: A systematic review and meta-analysis of randomized controlled trials. Prog Cardiovasc Dis. 2022;73:48-55. DOI:10.1016/j.pcad.2022.01.005.
12. Arutyunov GP, Drapkina OM, Kobalava ZhD, et al. The concept of fixed-dose combination drugs in primary and secondary prevention of cardiovascular disease. Position paper of the Russian Society of Cardiology, the Russian Society for the Prevention of Noncommunicable Diseases, the Russian Scientific Medical Society of Internal Medicine, the Russian Association of Endocrinologists, the Association of Clinical Pharmacologists, the Eurasian Association of Internal Medicine, the Russian Association of Gerontologists and Geriatricians. Russian Journal of Cardiology. 2024;29(9):6074. (In Russ.). DOI:10.15829/1560-4071-2024-6074.
13. Kolmakova TE, Alekseeva IA, Tmoyan NA, Ezhov MV. Combined hypolipidemic therapy with rosuvastatin and ezetimibe is the key to success in the treatment and prevention of cardiovascular diseases. Meditsinskiy Sovet. 2024;18(5):22-9. (In Russ.) DOI:10.21518/ms2024-124.
14. Bays HE, Davidson MH, Massaad R, et al. Safety and efficacy of ezetimibe added on to rosuvastatin 5 or 10 mg versus up-titration of rosuvastatin in patients with hypercholesterolemia (the ACTE Study). Am J Cardiol. 2011;108(4):523-30. DOI:10.1016/j.amjcard.2011.03.079.
15. Ballantyne CM, Weiss R, Moccetti T, et al. ; EXPLORER Study Investigators. Efficacy and safety of rosuvastatin 40 mg alone or in combination with ezetimibe in patients at high risk of cardiovascular disease (results from the EXPLORER study). Am J Cardiol. 2007;99(5):673-80. DOI:10.1016/j.amjcard.2006.10.022.
Supplementary files
Review
For citations:
Alekseeva I.A., Chubykina U.V., Ezhov M.V., Tyurina A.V., Kolmakova T.E., Tmoyan N.A., Sokolov A.A., Rozhkova T.A., Kurochkina N.S., Sergienko I.V., Avdeeva I.V., Oleynikov V.E., Alieva A.S., Androsyuk N.G., Kiselevа M.A., Grigorieva Yu.G., Asekritova A.S., Kylbanova E.S., Pavlova A.V., Ershova A.I., Meshkov A.N., Mikhailina V.I., Blokhina A.V., Limonova A.S., Kopylova O.V., Vorobyev A.S., Astrakhantseva I.D., Vorobyeva Yu.A., Ermakova Yu.A., Sadykova D.I., Slastnikova E.S., Galimovа L.F., Shaposhnik I.I., Genkel V.V., Egorova A.V., Mukha N.V., Vasilenko P.V., Zaitsev D.N., Kim Z.F., Zafiraki V.K., Zykov M.V., Korneva V.A., Kuznetsova T.Yu., Malyshenko Yu.A., Petelina T.I., Mikova E.V., Namitokov A.M., Kosmacheva E.D., Pshenichnikova I.I., Konstantinov V.O., Bednova S.E., Voevoda M.I., Timoshenko O.V., Ragino Yu.I., Filippov A.E., Tuktarov A.M., Gurevich V.S., Muzalevskaya M.V., Urazgildeevа S.A., Khokhlov R.A., Yarkovaya S.V., Shutemova E.A., Kudelkina E.V., Bizyaeva N.N. Effectiveness of fixed-dose combination of rosuvastatin and ezetimibe in heterozygous familial hypercholesterolemia from the RENAISSANCE registry. Rational Pharmacotherapy in Cardiology. 2025;21(3):244-256. (In Russ.) https://doi.org/10.20996/1819-6446-2025-3205. EDN: XSPXJN