Rational Pharmacotherapy in Cardiology

Advanced search


Full Text:


Aim. To evaluate the differences between a group of patients treated with ursodeoxycholic acid (UDCA) during the study period and a group of patients not treated with UDCA by pseudo-randomization using Propensity Score Matching.

Material and methods. 262 patients aged 60.1±8.9 years, taking statins for the secondary prevention of cardiovascular complications were included into a 6-month observational cohort study. The UDCA intake was recommended to all the patients due to the presence of liver and/or bile duct diseases. One part of the patients strictly followed medical recommendations and used UDCA, while the other part of the patients wasn’t taking UDCA. This allowed comparing the effect of UDCA in these groups.

Results. Propensity Score Matching method allowed forming two groups of patients of 52 people each with similar main clinical and demographic characteristics. A more significant decrease in the levels of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) (up to 4.0 mmol/L and 1.92 mmol/L, respectively; p<0.001) after 6 months was found in patients treated with lipid-lowering therapy in combination with UDCA as compared with patients without UDCA (up to 4.52 mmol/L and 2.6 mmol/L, respectively; p<0.05). No ALT, AST, CPK, LDH activity deterioration and no bilirubin serum level increase was found. Due to statin treatment the target levels of LDL-C by the end of the study were achieved in 31% of the patients of UDCA-group. Target levels of LDL-C were not achieved in any of the patients of the group without UDCA (p<0.001). There was demonstrated a high adherence to UDCA therapy.

Conclusion. Combined therapy with statins and UDCA is effective and safe in patients with high cardiovascular risk and concomitant liver disease. Co-administration of statins with UDCA is promising in the treatment of hyperlipidemia in patients with low tolerance to statins. However, additional controlled studies are required.

About the Authors

N. P. Kutishenko
State Research Centre for Preventive Medicine
Russian Federation
Petroverigsky per. 10, Moscow, 101990 Russia

S. Yu. Martsevich
State Research Centre for Preventive Medicine
Russian Federation
Petroverigsky per. 10, Moscow, 101990 Russia

O. V. Lerman
State Research Centre for Preventive Medicine
Russian Federation
Petroverigsky per. 10, Moscow, 101990 Russia

I. S. Balashov
State Research Centre for Preventive Medicine, I.M. Sechenov First Moscow State Medical University
Russian Federation

Petroverigsky per. 10, Moscow, 101990 Russia

Trubetskaya ul. 8-2, Moscow, 119991 Russia

V. A. Nevzorova
Vladivostok State Medical University
Russian Federation
Ostryakova pr. 2, Vladivostok, 690002 Russia

I. I. Reznik
Ural State Medical Academy
Russian Federation
Repina ul. 3, Ekaterinburg, 620028 Russia

G. V. Shavkuta
Rostov State Medical University
Russian Federation
Nakhichevanskii per., 29, Rostov-on-Don, 344022 Russia

D. A. Yakhontov
Novosibirsk State Medical University
Russian Federation

Krasnii prospekt 52, Novosibirsk, 630091 Russia


1. ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J 2011: 32; 1769-818.

2. Law M, Rudnicka AR. Statin safety: a systematic review. Am J Cardiol 2006; 97(Suppl): 52-60.

3. Alsheikh-Ali A.A., Maddukuri P.V., Han H., Karas R.H. Effect of the Magnitude of Lipid Lo-wering on Risk of Elevated Liver Enzymes, Rhabdomyolysis, and Cancer. Insights From Large Randomized Statin Trials. J Am Coll Cardiol 2007;50:409-18.

4. Sattar N, Preiss D, Murrary HM et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. The Lancet 2010; 375(9716): 735-42.

5. Beydoun MA, Beason-Held LL, Kitner-Triolo MH, et al. Statins and serum cholesterol's associa-tions with incident dementia and mild cognitive impairment. J Epidemiol Community Health 2011;65:949-57.

6. Macedo A.F., Taylor F.C., Casas J.F., Adler A. et al. Unintended effects of statins from observational studies in the general population: systematic review and meta-analysis. BMC Medicine 2014;12:51.

7. Yusuf S, Islam S, Chow CK, et al. Prospective Urban Rural Epidemiology (PURE) Study Investigators. Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middleincome, and low-income countries (the PURE Study): a prospective epidemiological survey. Lancet 2011; 378 :1231-43.

8. Martsevich SY, Kutishenko NP, Suvorov A., et al., On behalf of the working group LIS-2 study. Characteristics of patients with cerebral stroke or transient ischemic attack, included in the register of LIS-2 (Lyubertsy study of mortality in patients after cerebral stroke). Rational Pharmacotherapy in Cardiology 2015; 11 (1): 18-24. Russian (Марцевич С.Ю., Кутишенко Н.П., Суворов А.Ю., и др. от имени рабочей группы исследования «ЛИС-2». Характеристика пациентов с мозговым инсультом или транзиторной ишемической атакой, включенных в регистр ЛИС-2 (Люберецкое исследование смертности больных, перенесших мозговой инсульт). Рациональная Фармакотерапия в Кардиологии 2015;11(1):18-24).

9. Tolpygina SN, Polyanskaya YN, Martsevich SY. Lipid-lowering therapy in patients with chronic coronary heart disease in 2004-2010. According to the register "PROGNOZ IBS" Ration Pharmacother Cardiol 2015; 11 (1): 18-24. Russian (Толпыгина С.Н., Полянская Ю.Н., Марцевич С.Ю. Гиполипидемическая терапия у пациентов с хронической ишемической болезнью сердца в 2004-2010 гг. По данным регистра «ПРОГНОЗ ИБС». Рациональная Фармакотерапия в Кардиологии 2015;11(1):18-24).

10. Boytsov SA, Lukyanov MM, Jakushin SS, et al. Register cardiovascular disease (REKVAZA): diagnosis, concomitant cardiovascular disease, comorbidity and treatment in a real ambulatornopoliklinicheskoy practice. Kardiovaskulyarnaya Terapiya i Profilaktika 2014; (6): 44-50.Бойцов С.А., Лукьянов М.М., Якушин С.С., и др. Регистр кардиоваскулярных заболеваний (РЕКВАЗА): диагностика, сочетанная сердечнососудистая патология, сопутствующие заболевания и лечение в условиях реальной амбулаторно-поликлинической практики. Кардиоваскулярная Терапия и Профилактика 2014; (6): 44-50.

11. Drapkina OM. To a question about the safety of statins. Review of data. Ration Pharmacother Cardiol 2013; 9 (2): 143-8. Russian (Драпкина О.М. К вопросу о безопасности статинов. Обзор данных. Рациональная Фармакотреапия в Кардиологии 2013; 9(2): 143-8).

12. Martsevich SY, Lerman OV, Kutishenko NP, Suvorov AY. The problem of statins in patients with cardiovascular diseases and related liver diseases. What do think about it clinicians? Ration Pharmacother Cardiol 2015; 11 (2): 173-5. Russian (Марцевич С.Ю., Лерман О.В., Кутишенко Н.П., Суворов А.Ю. Проблема назначения статинов больным с сердечно-сосудистыми заболеваниями и сопутствующими болезнями печени. Что о ней думают практические врачи? Рациональная Фармакотерапия в Кардиологии 2015; 11(2): 173-5).

13. Onofrei M.D., Butler K.L., Fuke D.C., Miller H.B. Safety of statin therapy in patients with preexisting liver disease. Pharmacotherapy 2008;28(4):522-9.

14. Calderon R.M., Cubeddu L.X., Goldberg R.B., Schiff E.R. Statins in treatment of dyslipidemia in the presence of elevated liver aminotransferase levels: a therapeutic dilemma. Mayo Clin Proc 2010; 85(4):349-356.

15. Cueto R., Valdivielso P., Lucena M.I., et al. Statins: Hepatic disease and hepato-toxicity risk. The Open Gastroenterology Journal 2008; 2: 18-23.

16. McKenney J.M., Davidson M.H., Jacobson T.A., Guyton J.R. Final Conclusions and Recom-mendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Car-diol 2006; 97(suppl): 89-94.

17. Lipitor (atorvastatin Calcium Tablets). Information on medications. Available at: Accessed by 20.06.2015

18. Korneeva ON, Drapkina OM. Applications ursodizoksiholevoy kitty items and statins to reduce cardiovascular risk in patients with metabolic syndrome and nonalcoholic fatty liver disease. Rossiyskie Meditsinskie Vesti 2011; 16 (3): 57-64. Russian (Корнеева О.Н., Драпкина О.М. Возможности применения урсодизоксихолевой кислоты и статинов для уменьшения сердечно-сосудистого риска у больных с метаболическим синдромом и неалкогольной жировой болезнью печени. Российские Медицинские Вести 2011; 16 (3): 57-64).

19. Kiyici M., Gulten M., Gurel S., еt аl. Ursodeoxycholic acid and atorvastatin in the treatment of nonalcoholic steatohepatitis. Can J Gastroenterol 2003;17(12):713-8.

20. Cabezas GR. Effect of ursodeoxycholic acid combined with statins in hypercholesterolemia treatment: a prospective clinical trial. Rev Clin Esp 2004; 204(12): 632-5.

21. Korneeva ON, Drapkina OM. How to avoid the appointment of statin hepatotoxicity in patients with obesity and hepatic pathology? Focus on a combination of ursodeoxycholic acid and atorvastatin. Kardiovaskulyarnaya Terapiya i Profilaktika 2012; 11 (6): 81-4. Russian (Корнеева О.Н., Драпкина О.М. Как избежать гепатотоксичности при назначении статинов у пациентов с ожирением и сопутствующей патологией печени? Фокус на комбинацию урсодезоксихолевой кислоты и аторвастатина. Кардиоваскулярная Терапия и Профилактика 2012; 11(6): 81-4).

22. Martsevich SY, Kutishenko NP, Drozdova LY, et al. The influence of ursodez-oksiholevoy acid on the efficacy and safety of statin therapy in patients with diseases of the liver, gallbladder and / or bile ducts (the RAKURS study). Ration Pharmacother Cardiol 2014; 10 (2): 147-52. Russian (Марцевич С.Ю., Кутишенко Н.П., Дроздова Л.Ю., и др. Изучение влияния урсодезоксихолевой кислоты на эффективность и безопасность терапии статинами у больных с заболеваниями печени, желчного пузыря и/или желчевыводящих путей (исследование РАКУРС). Рациональная Фармакотерапия в Кардиологии 2014; 10(2): 147-52).

23. Martsevich SY, Kutishenko NP, Drozdova LY, et al. Study ANGLE: in improving the efficiency and safety of statin therapy in patients with diseases of the liver-ne, gall bladder and / or bile ducts with using ursodeoxycholic kitty lots. Terapevticheskiy Arkhiv 2014; 12: 48-52. Russian (Марцевич С.Ю., Кутишенко Н.П., Дроздова Л.Ю., и др. Исследование РАКУРС: повышение эффективности и безопасности терапии статинами у больных с заболеваниями печени, желчного пузыря и/или желчевыводящих путей с помощью урсодезоксихолевой кислоты. Терапевтический Архив 2014; 12: 48-52).

24. Lauer M.S., D’Agostino R.B. The randomized registry trial – the next disruptive technology in clinical research? N Engl Med 2013; 363(17): 1579-1581.

25. D’Agostino R.B. Tutorial in biostatistics propensity score methods for bias reduction in the comparison of a treatment to а non-randomized control group. Statist Med 1998; 17: 2265-81.

26. Poupon RE, Ouguerram K, Chrétien Y, et al. Cholesterol-lowering effect of ursodeoxycholic acid in patients with primary biliary cirrhosis. Hepatology 1993;17(4):577-82.

27. Bhardwaj S., Chalasani N. Lipid lowering agents that cause drug-induced hepatotoxicity. Clin Liver Dis 2007; 11(3): 597-614.


For citations:

Kutishenko N.P., Martsevich S.Yu., Lerman O.V., Balashov I.S., Nevzorova V.A., Reznik I.I., Shavkuta G.V., Yakhontov D.A. THE IMPROVEMENT OF LIPID-LOWERING THERAPY EFFECTIVENESS IN PATIENTS WITH HIGH CARDIOVASCULAR RISK AND CONCOMITANT LIVER DISEASE (RESULTS OF ADDITIONAL ANALYSIS OF THE RAKURS STUDY). Rational Pharmacotherapy in Cardiology. 2015;11(3):297-303. (In Russ.)

Views: 691

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

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