Rational Pharmacotherapy in Cardiology

Advanced search


Full Text:


Aim. To assess the potential of ursodeoxycholic acid (UDCA) in the prevention of liver dysfunction in patients with cardiovascular diseases (CVD) and high risk of cardiovascular events (CVE) with indications for statins use.

Material and methods. Patients (n=262, age 60.1±8.9 years) took statins for secondary prevention of CVE in observational cohort study. The follow-up duration was 6 months. UDCA was recommended for all patients because of liver diseases and/or biliary tract. Some of the patients with high treatment compliance strictly followed recommendations to take UDCA, and another part of the patients with low treatment compliance did not take UDCA. Comparison of these groups allowed highlighting UDCA effects.

Results. Controlled lipid-lowering therapy in combination with UDCA resulted in a significant reduction in total cholesterol (TC) and low density lipoprotein cholesterol levels after 6 months of follow-up to 4.3 mmol/L and 2.3 mmol/L, respectively (p<0.001). Deterioration in the dynamics of alanine-aminotransferase (ALT), aspartate aminotransferase (AST), creatinphosphokinase (CPK) and gamma glutamine transferase (GGT), as well as increase in serum bilirubin was not found. Moreover, in general significant decrease in ALT, AST, GGT and alkaline phosphatase (p<0.001) was observed, the levels of total serum bilirubin and CPK did not change at the end of the study (p=0.65 and p=0.16, respectively). Taking UDCA simultaneously with statins led to additional reduction in TC and low density cholesterol compared with statin monotherapy (p=0.01).

Conclusion. One of the affordable and effective ways to deal with a wider statin use in patients with liver and biliary tract disorders is their co-administration with UDCA.

About the Authors

S. Yu. Martsevich
State Research Center for Preventive Medicine, Moscow
Russian Federation

N. P. Kutishenko
State Research Center for Preventive Medicine, Moscow
Russian Federation

L. Yu. Drozdova
State Research Center for Preventive Medicine, Moscow
Russian Federation

O. V. Lerman
State Research Center for Preventive Medicine, Moscow
Russian Federation

V. A. Nevzorova
Pacific State Medical University, Vladivostok
Russian Federation

I. I. Reznik
Ural State Medical Academy, Ekaterinburg
Russian Federation

G. V. Shavkuta
Rostov State Medical University, Rostov-on-Don
Russian Federation

D. A. Yahontov
Novosibirsk State Medical University
Russian Federation


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 Lowering 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. Lancet 2010; 375(9716): 735-42.

5. Beydoun MA, Beason-Held LL, Kitner-Triolo MH, et al. Statins and serum cholesterol's associations with incident dementia and mild cognitive impairment. J Epidemiol Community Health 2011;65:94957.

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. Drapkina OM, Gatsolaeva DS, Ivashkin VT. Nonalcoholic fatty liver disease as a component of the metabolic syndrome. Russian Medical News 2010; (2): 72-8. Russian (Драпкина О.М., Гацолаева Д.С., Ивашкин В.Т.Неалкогольная жировая болезнь печени как компонент метаболического синдрома. Российские Медицинские Вести 2010; (2): 72-8).

8. 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.

9. Cohen DE, Anania FA, Chalasani N; for the National Lipid Association Statin Safety Task Force Liver Expert Panel. An assessment of statin safety by hepatologists. Am J Cardiol 2006;97(8A):77C-81C.

10. 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):349-56.

11. Cueto R., Valdivielso P., Lucena M.I., Carcia-Arias N.B. et al. Statins: Hepatic disease and hepatotoxicity risk. The Open Gastroenterology Journal 2008; 2: 18-23.

12. McKenney J.M., Davidson M.H., Jacobson T.A., Guyton J.R. Final Conclusions and Recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol 2006; 97[suppl]:89-94.

13. Korneeva ON, Drapkina OM. Possible applications ursodizoksiholevoy acid and statins to reduce cardiovascular risk in patients with metabolic syndrome and nonalcoholic fatty liver disease. Russian Medical News 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).

14. 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.

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

16. The national guidelines for the diagnosis and correction of lipid ex-change for the prevention and treatment of atherosclerosis (IV revision). Cardiovascular Therapy and Prevention 2009; 6 suppl 3: 1-58. Russian (Национальные рекомендации по диагностике и коррекции нарушений липидного обмена с целью профилактики и лечения атеросклероза (IV пересмотр). Кардиоваскулярная Терапия и Профилактика 2009; 6 Приложение 3: 1-58).

17. The efficacy and safety of drug therapy in primary and secondary prevention of cardiovascular diseases. Cardiovascular Therapy and The prevention, 2009; 6 Appendix 4: 1-56. Russian (Эффективность и безопасность лекарственной терапии при первичной и вторичной профилактике сердечно-сосудистых заболеваний. Кардиоваскулярная Терапия и Профилактика 2009; 6 Приложение 4: 1-56).

18. Lauer M.S., D’Agostino R.B. The randomized registry trial – the next disruptive technology in clinical research? N Engl Med 2013; 363(17): 1579-81.

19. Boytsov SA, Martsevich SYu, Kutishenko NP, Drozdova LY. Registers in cardiology. Basic rules of conduct and a real opportunity. Cardiovascular Therapy and Prevention 2013; 12 (1): 4-9. Russian (Бойцов С.А., Марцевич С.Ю., Кутишенко Н.П., Дроздова Л.Ю. Регистры в кардиологии. Основные правила проведения и реальные возможности. Кардиоваскулярная Терапия иПрофилактика 2013; 12(1): 4-9).

20. Martsevich SY, Drozdova LY, Kutishenko NP, Ginsburg ML. Registers as a way to study the effectiveness and safety of drugs. Clinician 2012; (3-4): 4-10. Russian (Марцевич С.Ю., Дроздова Л.Ю., Кутишенко Н.П., Гинзбург М.Л. Регистры как способ изучения эффективности и безопасности лекарственных препаратов. Клиницист 2012; (3-4): 4-10).

21. Drapkina OM, Ashihmin YI, Ivashkin VT. Statins and liver: friend or foe? A Critical Review. Heart 2011; 10 (1): 38-42. Russian (Драпкина О.М., Ашихмин Я.И., Ивашкин В.Т. Статины и печень: друзья или враги? Критический обзор. Сердце 2011; 10 (1): 38-42).

22. Bhardwaj S.S., Chalasani N. Lipid lowering Agents That Cause Drug-Induced Hepatotoxicity. Clin Liver Dis 2007; 11(3): 597-614.

23. Silva M., Matthews M.L., Jarvis C., et al. Meta-analysis of drug-induced adverse events associated with intensive-dose statin therapy. Clin Ther 2007; 29(2): 253-60.

24. Martsevich SY, Drozdova LY, Lukina YV, et al. As clinicians evaluate the possibilities of modern medical therapy in patients with chronic ischemic heart disease. The results of the poll in Moscow and Voronezh. Ration Pharmacother Cardiol 2010; 6 (2): 145-8. Russain (Марцевич С.Ю., Дроздова Л.Ю., Лукина Ю.В., и др. Как оценивают практические врачи возможности современной медикаментозной терапии больных хронической ишемической болезнью сердца. Результаты опросов в Москве и Воронеже. Рациональная Фармакотерапия в Кардиологии 2010; 6 (2): 145-8).

25. Lipson A., Fallis W., Wang X.,Yi Y. Are patients with hyperlipidemia undertreated? Canadian Family Physician 2007; 53: 1503-1507.

26. Julian D. Translation of clinical trials into clinical practice. Journal of Internal Medicine 2004; 255: 309-316.

27. Martsevich SY, Gaisenok OV, Tripkosh SG, et al. Real practice of prescribing statins and its dependence on the observations in the prefecture of specialized medical center for patients with high risk of cardiovascular complications (according to the PROFIL register). Ration Pharmacother Cardiol 2013; 9 (4): 362-7. Russian (Марцевич С.Ю., Гайсенок О.В., Трипкош С.Г., и др. Реальная практика назначения статинов и ее зависимость от наблюдения в специализированном медицинском центре у больных с высоким риском сердечно-сосудистых осложнений (по данным регистра ПРОФИЛЬ). Рациональная Фармакотерапия в Кардиологии 2013; 9 (4): 362-7).

28. Jin J., Sklar G.E., Oh M.N.S., Li S.C. Factors affecting therapeutics compliance: A review from patient’s perspective. Ther Clin Risk Manag 2008; 4(1): 269-86.

29. Argo CK, Loria P, Caldwell SH, Lorando A. Statins in disease: a molehill, an iceberg, or neither. Hepatology 2008; 48(2): 662-9.

30. Tzefos M, Olin JL. 3-hydroxyl-3-methylglutaril coenzyme A reductase inhibitor use in chronic liver disease: a therapeutic controversy. J Clin Lipidol 2011; 5(6): 450-9.


For citations:

Martsevich S.Yu., Kutishenko N.P., Drozdova L.Yu., Lerman O.V., Nevzorova V.A., Reznik I.I., Shavkuta G.V., Yahontov D.A. STUDY OF URSODEOXYCHOLIC ACID INFLUENCE ON EFFICACY AND SAFETY OF STATIN THERAPY IN PATIENTS WITH DISEASES OF THE LIVER, GALL BLADDER AND/OR BILIARY TRACT (THE RAKURS STUDY). Rational Pharmacotherapy in Cardiology. 2014;10(2):147-152. (In Russ.)

Views: 1056

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

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