Preview

Rational Pharmacotherapy in Cardiology

Advanced search

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.

About the Authors

I. A. Alekseeva
E. I. Chazov National Medical Research Center of Cardiology
Russian Federation

Irina A. Alekseeva 

Moscow



U. V. Chubykina
E. I. Chazov National Medical Research Center of Cardiology
Russian Federation

Uliana V. Chubykina 

Moscow



M. V. Ezhov
E. I. Chazov National Medical Research Center of Cardiology
Russian Federation

Marat V. Ezhov 

Moscow



A. V. Tyurina
E. I. Chazov National Medical Research Center of Cardiology
Russian Federation

Aleksandra V. Tyurina 

Moscow



T. E. Kolmakova
E. I. Chazov National Medical Research Center of Cardiology
Russian Federation

Tatiana E. Kolmakova 

Moscow



N. A. Tmoyan
E. I. Chazov National Medical Research Center of Cardiology
Russian Federation

Narek A. Tmoyan 

Moscow



A. A. Sokolov
E. I. Chazov National Medical Research Center of Cardiology
Russian Federation

Alexey A. Sokolov 

Moscow



T. A. Rozhkova
E. I. Chazov National Medical Research Center of Cardiology
Russian Federation

Tatiana A. Rozhkova 

Moscow



N. S. Kurochkina
E. I. Chazov National Medical Research Center of Cardiology
Russian Federation

Natalia S. Kurochkina

Moscow



I. V. Sergienko
E. I. Chazov National Medical Research Center of Cardiology
Russian Federation

Igor V. Sergienko 

Moscow



I. V. Avdeeva
Penza State University
Russian Federation

Irina V. Avdeeva 

Penza



V. E. Oleynikov
Penza State University
Russian Federation

Valentin E. Oleynikov 

Penza



A. S. Alieva
Almazov National Medical Research Center
Russian Federation

Asiiat S. Alieva 

St. Petersburg



N. G. Androsyuk
Astrakhan State Medical University ; Regional Clinical Cardiology Dispensary
Russian Federation

Natalia G. Androsyuk 

Astrakhan



M. A. Kiselevа
Astrakhan State Medical University ; Regional Clinical Cardiology Dispensary
Russian Federation

Maria A. Kiselevа 

Astrakhan



Yu. G. Grigorieva
Astrakhan State Medical University ; Region Alexander-Mariinsky Regional Clinical Hospital
Russian Federation

Yulia G. Grigorieva 

Astrakhan



A. S. Asekritova
Republican Clinical Hospital № 3 ; M. K. Ammosov North-Eastern Federal University
Russian Federation

Aleksandra S. Asekritova 

Yakutsk



E. S. Kylbanova
M. K. Ammosov North-Eastern Federal University
Russian Federation

Elena S. Kylbanova 

Yakutsk 



A. V. Pavlova
Republican Clinical Hospital № 3 ; Kurgan Regional Clinical Hospital
Russian Federation

Anna V. Pavlova 

Yakutsk; Kurgan



A. I. Ershova
National Medical Research Center for Therapy and Preventive Medicine
Russian Federation

Alexandra I. Ershova

Moscow



A. N. Meshkov
E. I. Chazov National Medical Research Center of Cardiology ; National Medical Research Center for Therapy and Preventive Medicine
Russian Federation

Aleksey N. Meshkov

Moscow



V. I. Mikhailina
National Medical Research Center for Therapy and Preventive Medicine
Russian Federation

Viktoria I. Mikhailina 

Moscow



A. V. Blokhina
National Medical Research Center for Therapy and Preventive Medicine
Russian Federation

Anastasia V. Blokhina 

Moscow



A. S. Limonova
National Medical Research Center for Therapy and Preventive Medicine
Russian Federation

Alena S. Limonova 

Moscow



O. V. Kopylova
National Medical Research Center for Therapy and Preventive Medicine
Russian Federation

Oksana V. Kopylova

Moscow



A. S. Vorobyev
District Cardiological Dispensary Center for Diagnostics and Cardiovascular Surgery
Russian Federation

Anton S. Vorobyev 

Surgut



I. D. Astrakhantseva
District Cardiological Dispensary Center for Diagnostics and Cardiovascular Surgery
Russian Federation

Irina D. Astrakhantseva 

Surgut



Yu. A. Vorobyeva
Altai Regional Cardiology Dispensary
Russian Federation

Yulia A. Vorobyeva 

Barnaul



Yu. A. Ermakova
Altai Regional Cardiology Dispensary
Russian Federation

Yulia A. Ermakova 

Barnaul



D. I. Sadykova
Kazan State Medical University
Russian Federation

Dinara I. Sadykova 

Kazan



E. S. Slastnikova
Kazan State Medical University
Russian Federation

Evgeniia S. Slastnikova 

Kazan



L. F. Galimovа
Kazan State Medical University ; Republican Children’s Clinical Hospital
Russian Federation

Lily F. Galimovа 

Kazan



I. I. Shaposhnik
South Ural State Medical University
Russian Federation

Igor I. Shaposhnik 

Chelyabinsk



V. V. Genkel
South Ural State Medical University
Russian Federation

Vadim V. Genkel 

Chelyabinsk



A. V. Egorova
Samara City clinic № 1
Russian Federation

Antonina V. Egorova 

Samara



N. V. Mukha
Chita State Medical Academy
Russian Federation

Natalia V. Mukha 

Chita



P. V. Vasilenko
Chita State Medical Academy
Russian Federation

Pavel V. Vasilenko

Chita



D. N. Zaitsev
Irkutsk State Medical University
Russian Federation

Dmitry N. Zaitsev 

Irkutsk



Z. F. Kim
Kazan State Medical University ; M. N. Sadykov City Clinical Hospital № 7
Russian Federation

Zulfiya F. Kim 

Kazan



V. K. Zafiraki
Kuban State Medical University
Russian Federation

Vitaliy K. Zafiraki 

Krasnodar



M. V. Zykov
Sochi City Hospital № 4
Russian Federation

Mikhail V. Zykov 

Sochi



V. A. Korneva
Petrozavodsk State University
Russian Federation

Viktoria A. Korneva

Petrozavodsk



T. Yu. Kuznetsova
Petrozavodsk State University
Russian Federation

Tatiana Yu. Kuznetsova

Petrozavodsk



Yu. A. Malyshenko
Immanuel Kant Baltic Federal University
Russian Federation

Yulia A. Malyshenko 

Kaliningrad



T. I. Petelina
Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Sciences
Russian Federation

Tatiana I. Petelina 

Tomsk



E. V. Mikova
Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Sciences
Russian Federation

Ekaterina V. Mikova 

Tomsk



A. M. Namitokov
S. V. Ochapovsky Regional Clinical Hospital № 1
Russian Federation

Alim M. Namitokov 

Krasnodar



E. D. Kosmacheva
S. V. Ochapovsky Regional Clinical Hospital № 1
Russian Federation

Elena D. Kosmacheva

Krasnodar



I. I. Pshenichnikova
Russian Medical Academy of Continuous Professional Education ; Z. A. Bashlyaeva Children’s City Clinical Hospital ; Research Institute for Healthcare Organization and Medical Management
Russian Federation

Irina I. Pshenichnikova

Moscow 



V. O. Konstantinov
War Veterans Hospital
Russian Federation

Vladimir O. Konstantinov

Saint Petersburg

 



S. E. Bednova
S. M. Kirov Military medical academy
Russian Federation

Svetlana E. Bednova

Saint Petersburg



M. I. Voevoda
Research Institute of Therapy and Preventive Medicine — Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation

Mikhail I. Voevoda

Novosibirsk



O. V. Timoshenko
Research Institute of Therapy and Preventive Medicine — Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation

Olga V. Timoshenko 

Novosibirsk



Yu. I. Ragino
Research Institute of Therapy and Preventive Medicine — Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation

Yulia I. Ragino

Novosibirsk



A. E. Filippov
My Medical Center ; Saint Petersburg State University
Russian Federation

Alexandr E. Filippov 

Saint Petersburg



A. M. Tuktarov
My Medical Center ; Saint Petersburg State University
Russian Federation

Artur M. Tuktarov 

Saint Petersburg



V. S. Gurevich
Saint Petersburg State University ; I. I. Mechnikov North-Western State Medical University ; L. G. Sokolov North-Western district scientific and clinical center
Russian Federation

Victor S. Gurevich 

Saint Petersburg 



M. V. Muzalevskaya
Saint Petersburg State University ; L. G. Sokolov North-Western district scientific and clinical center
Russian Federation

Maria V. Muzalevskaya 

Saint Petersburg



S. A. Urazgildeevа
Saint Petersburg State University ; L. G. Sokolov North-Western district scientific and clinical center
Russian Federation

Soreya A. Urazgildeevа 

Saint Petersburg



R. A. Khokhlov
N. N. Burdenko Voronezh State Medical University ; Voronezh Regional Clinical Advisory and Diagnostic Center
Russian Federation

Roman A. Khokhlov 

Voronezh



S. V. Yarkovaya
Voronezh Regional Clinical Advisory and Diagnostic Center
Russian Federation

Svetlana V. Yarkovaya 

Voronezh



E. A. Shutemova
Cardiology Dispensary
Russian Federation

Elena A. Shutemova 

Ivanovo



E. V. Kudelkina
Kurgan Regional Clinical Hospital
Russian Federation

Ekaterina V. Kudelkina 

Kurgan



N. N. Bizyaeva
Clinical Cardiology Dispensary
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

Views: 18


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)