2016


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2016/№4

KUDESan® (3% drops for oral use) in treatment of patieNts with heart failure: efficacy and safety In Combination with standard therapy (KUDESNIC). Design and results of a prospective, randomized, double-blind KUDESNIC study

Mareev V.Yu.1, Minina Yu.V.2, Begrambekova Yu.L.1
1 – Federal State Budgetary Educational Institution of Higher Professional Education, "M.V. Lomonosov Moscow State University ", Leninskie Gory 1, GSP-1, Moscow 119991
2 – All-Russian Public Organization, "Society of Experts in Heart Failure", Moscow, info@ossn.ru

Keywords: Kudesan, coenzyme Q10, safety, efficacy, treatment, CHF

DOI: 10.18087/rhfj.2016.4.2257

Background. In addition to the standard therapy for CHF, a possible option for influencing symptoms and quality of life is acting on myocardial metabolism. One of cardioprotectors recommended for CHF treatment is coenzyme Q10, which reduces intensity of oxidative stress at the molecular level and possesses antioxidant properties. Aim. To evaluate clinical efficacy and safety of the drug Kudesan® in the dosage form of 3% oral drops as a part of multimodal therapy for CHF in the real practice setting. Materials and methods. The study included 148 patients aged 50 to 70 with FC II-III CHF. All patients received 3 ml of 3% Kudesan® solution (equivalent to Kudesan 90 mg per day) or placebo. Thorough clinical examination, including ECG, two-dimensional EchoCG (extended examination), 6-min walk test, CHF FC determination, clinical condition evaluation using the Clinical Condition Scale (CCS), evaluation of quality of life using different scales and questionnaires, measurement of blood BNP and coenzyme Q10, and recording the number of hospitalizations for decompensated CHF, were performed for all patients before and 6 months after the treatment. Safety was evaluated by records of adverse events (AEs) and changes in laboratory test results. Results. Study results demonstrated Kudesan® efficacy as evidenced by improved functional condition of patients, a significant increase in 6-min walk distance, improved CHF FC, a greater decrease in the CCS total score, a significant increase in LV EF, reduced dimensions of heart chambers, a tendency to decrease in BNP, and significant improvements in several parameters of quality of life. Analysis of all AEs ranged by their severity and relationship with the Kudesan® treatment showed good tolerability of Kudesan®. Conclusion. The study has demonstrated that Kudesan® is capable to considerably improve effects of the standard therapy for CHF.
1. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH et al. 2013 ACCF/AHA Guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Circulation. 2013 Oct 15;128(16):e240-327.
2. Cleland JG, Swedberg K, Follath F, Komajda M, Cohen-Solal A, Aguilar JC et al. The EuroHeart Failure survey programme - a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis. Eur Heart J. 2003 Mar;24(5):442–63.
3. Mosterd A, Hoes AW. Clinical epidemiology of heart failure. Heart. 2007 Sep;93(9):1137–46.
4. Беленков Ю.Н., Мареев В.Ю., Агеев В.Ю., Фомин И.В., Хохлов Р.А., Галявич А.С. и др. Первые результаты Российского эпидемиологического исследования по ХСН. Журнал Сердечная Недостаточность. 2003;4(1):17-18 [Belenkov Yu.N., Mareev V.Yu., Ageev V.Yu., Fomin I.V., Xoxlov R .A., Galyavich A.S. i dr. Pervy`e rezul`taty` Rossijskogo e`pidemiologicheskogo issledovaniya po XSN. Zhurnal Serdechnaya Nedostatochnost`. 2003;4 (1):17–8].
5. Агеев Ф.Т., Даниелян М.О., Мареев В.Ю., Беленков Ю.Н. Больные с хронической сердечной недостаточностью в российской амбулаторной практике: особенности контингента, диагностики и лечения (по материалам исследования ЭПОХА–О–ХСН). Журнал Сердечная Недостаточность. 2004;5(1):4–7 [Ageev F.T., Danielyan M.O., Mareev V.
Yu., Belenkov Yu.N. Bol`ny`e s xronicheskoj serdechnoj nedostatochnost`yu v rossijskoj ambulatornoj praktike: osobennosti kontingenta, diagnostiki i lecheniya (po materialam issledovaniya E`POXA–O–XSN). Zhurnal Serdechnaya Nedostatochnost`. 2004;5 (1):4–7].
6. Агеев Ф.Т., Беленков Ю.Н., Фомин И.В., Мареев В.Ю., Бадин Ю.В., Галявич А.С. и др. Распространенность хронической сердечной недостаточности в Европейской части Российской Федерации – данные ЭПОХА–ХСН. Журнал Сердечная Недостаточность. 2006;7(1):4–7 [Ageev F.T., Belenkov Yu.N., Fomin I.V., Mareev V.Yu., Badin Yu.V., Galyavich A.S. i dr. Rasprostranennost` xronicheskoj serdechnoj nedostatochnosti v Evropejskoj chasti Rossijskoj Federaczii – danny`e E`POXA-XSN. Zhurnal Serdechnaya Nedostatochnost`. 2006;7 (1):4–7].
7. Neubauer S. The failing heart — an engine out of fuel. N Engl J Med. 2007 Mar 15;356(11):1140-51.
8. Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003 Oct 15;552(Pt 2):335–44.
9. Chen Q, Vazquez EJ, Moghaddas S, Hoppel CL, Lesnefsky EJ. Production of reactive oxygen species by mitochondria: central role of complex III. J Biol Chem. 2003 Sep 19;278(38):36027–31.
10. Madamanchi NR, Runge MS. Mitochondrial dysfunction in atherosclerosis. Circ Res. 2007 Mar 2;100(4):460–73.
11. Sharma A, Fonarow GC, Butler J, Ezekowitz JA, Felker GM. Coenzyme Q10 and Heart Failure. A State-of-the-Art Review. Circ Heart Fail. 2016 Apr;9 (4):e002639.
12. Bentinger M, Brismar K, Dallner G. The antioxidant role of coenzyme Q.
Mitochondrion. 2007 Jun;7(Suppl):S41–50.
13. Forsmark P, Aberg F, Norling B, Nordenbrand K, Dallner G, Ernster L. Inhibition of lipid peroxidation by ubiquinol in submitochondrial particles in the absence of vitamin E. FEBS Lett. 1991 Jul 8;285(1):39–43.
14. Stocker R, Bowry VW, Frei B. Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol. Proc Natl Acad Sci USA. 1991 Mar 1;88(5):1646–50.
15. Forsmark-Andree P, Ernster L. Evidence for a protective effect of endogenous ubiquinol against oxidative damage to mitochondrial protein and DNA during lipid peroxidation. Mol Aspects Med. 1994;15(Suppl):s73–81.
16. Littarru GP, Ho L, Folkers K. Deficiency of coenzyme Q10 in human heart disease. Part I and Part II. Int J Vitam Nutr Res. 1972;42(2):291–305;(3):413–34.
17. Folkers K, Vadhanavikit S, Mortensen SA. Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10. Proc Natl Acad Sci USA. 1985 Feb;82(3):901–4.
18. Sunamori M, Tanaka H, Maruyama T, Sultan I, Sakamoto T, Suzuki A. Clinical experience of coenzyme Q10 to enhance intraoperative myocardial protection in coronary artery revascularization. Cardiovasc Drugs Ther. 1991 Mar;5(Suppl 2):297–300.
19. Molyneux SL, Florkowski CM, George PM, Pilbrow AP, Frampton CM, Lever M, Richards AM. Coenzyme Q10: an independent predictor of mortality in chronic heart failure. J Am Coll Cardiol. 2008 Oct 28;52(18):1435–41.
20. McMurray JJ, Dunselman P, Wedel H, Cleland JG, Lindberg M, Hjalmarson A et al. Coenzyme Q10, rosuvastatin, and clinical outcomes in heart failure: a pre-specified substudy of CORONA (Controlled Rosuvastatin Multinational Study in heart failure). J Am Coll Cardiol. 2010 Oct 5;56(15):1196–204.
21. Belardinelli R, Muçaj A, Lacalaprice F, Solenghi M, Seddaiu G, Principi F et al. Coenzime Q10 and exercise training in chronic heart failure. Eur Heart J. 2006 Nov;27(22):2675-81.
22. Sander S, Coleman CI, Patel AA, Kluger J, White CM. The impact of coenzyme Q10 on systolic function in patients with congestive heart failure. J Card Fail. 2006 Aug;12(6):464–72.
23. Baggio E, Gandini R, Plancher AC, Passeri M, Carmosino G. Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. CoQ10 Drug Surveillance Investigators. Mol Aspects Med. 1994;15(Suppl):s287-94.
24. Keogh A, Fenton S, Leslie C, Aboyoun C, Macdonald P, Zhao YC et al. Randomized double-blind, placebo-controlled trial of coenzyme Q10 therapy in class II and III systolic heart failure. Heart Lung Circ. 2003;12(3):135–41.
25. Mortensen SA. Perspectives on therapy of cardiovascular diseases with coenzyme Q10 (ubiquinone). Clin Investig. 1993;71(8 Suppl):S116–23.
26. Langsjoen PH, Folkers K, Lyson K, Muratsu K, Lyson T, Langsjoen P. Effective and safe therapy with coenzyme Q10 for cardiomyopathy. Klin Wochenschr. 1988 Jul 1;66(13):583–90.
27. Langsjoen PH, Folkers K. Long-term efficacy and safety of coenzyme Q10 therapy for idiopathic dilated cardiomyopathy. Am J Cardiol. 1990 Feb 15;65(7):521–3.
28. Morisco C, Trimarco B, Condorelli M. Effect of coenzyme Q10 therapy in patients with congestive heart failure: a long-term multicenter randomized study. Clin Investig. 1993;71(8 Suppl):S134–6.
29. Fotino AD, Thompson-Paul AM, Bazzano LA. Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis. Am J Clin Nutr. 2013 Feb;97 (2):268–75.
30. Каленикова Е.И., Городецкая Е.А., Медведев О.С. Биодоступность коэнзима Q10 в различных лекарственных формах. Химико–фармацевтический журнал. 2009;43(8):46–9 [Kalenikova E.I., Gorodeczkaya E.A., Medvedev O.S. Biodostupnost` koe`nzima Q10 v razlichny`x lekarstvenny`x formax. Ximiko-farmaczevticheskij zhurnal. 2009;43 (8):46–9].
31. Gorodetskaya E, Kalenikova E, Medvedev O. Increase of coenzyme Q10 level in rat myocardium after single administration of nanotechnologically prepared coenzyme Q10. J Hypertens. 2009;(Suppl 4):S139.
32. Li RK, Sole MJ, Mickle DA. Vitamin E and oxidative stress in the heart of the cardiomyopathic Syrian hamster. Free Radic Biol Med. 1998 Jan 15;24(2):252–8.
33. Keith M, Geranmayegan A, Sole MJ, Kurian R, Robinson A, Omran AS, Jeejeebhoy KN. Increased oxidative stress in patients with congestive heart failure. J Am Coll Cardiol. 1998 May;31(6):1352–6.
34. McMurray JJ, Chopra M, Abdullah I, Smith WE, Dargie HJ. Evidence of oxidative stress in chronic heart failure in humans. Eur Heart J. 1993 Nov;14(11):1493-8.
35. Медведев О.С. Замедление процессов старения: в фокусе коэнзим Q10. Трудный пациент. 2012;10(4):50-60 [Medvedev O.S. Zamedlenie proczessov stareniya: v fokuse koe`nzim Q10. Trudny`j paczient. 2012;10 (4):50–60].
36. Беленков Ю.Н., Привалова Е.В., Данилогорская Ю.А., Железных Е.А., Князева Л.В., Сергеева Е.А. Оксидативный стресс при хронической сердечной недостаточности. Возможности фармакологической коррекции. Кардиология и сердечно-сосудистая хирургия. 2009;2(1):4-9 [Belenkov Yu.N., Privalova E.V., Danilogorskaya Yu.A., Zhelezny`x E. A., Knyazeva L.V., Sergeeva E.A. Oksidativny`j stress pri xronicheskoj serdechnoj nedostatochnosti. Vozmozhnosti farmakologicheskoj korrekczii. Kardiologiya i serdechno-sosudistaya xirurgiya. 2009;2 (1):4–9].
37. Gorski PA, Ceholski DK, Hajjar RJ. Altered myocardial calcium cycling and energetics in heart failure – a rational approach for disease treatment. Cell Metab. 2015 Feb 3;21(2):183-94.
38. Fotino AD, Thompson-Paul AM, Bazzano LA. Effect of coenzyme Q10 supplementation on heart failure: a meta-analysis. Am J Clin Nutr. 2013 Feb;97(2):268–75.
39. Pourmoghaddas M, Rabbani M, Shahabi J, Garakyaraghi M, Khanjani R, Hedayat P. Combination of atorvastatin/coenzyme Q10 as adjunctive treatment in congestive heart failure: a double-blind randomized placebo-controlled clinical trial. ARYA Atheroscler. 2014 Jan;10(1):1–5.
40. Watson PS, Scalia GM, Galbraith A, Burstow DJ, Bett N, Aroney CN. Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure. J Am Coll Cardiol. 1999 May;33(6):1549–52.
41. Khatta M, Alexander BS, Krichten CM, Fisher ML, Freudenberger R, Robinson SW, Gottlieb SS. The effects of coenzyme Q10 in patients with congestive heart failure. Ann Intern Med. 2000 Apr 18;132(8):636–40.
42. Сизова Ж.М., Фарафонова Т.Н., Медведев О.С., Каленикова Е.И., Коротаева А.Л. Возможности применения различных доз коэнзима Q10 у больных хронической сердечной недостаточностью. Журнал Сердечная Недостаточность. 2010;11(4):218-23 [Sizova Zh.M., Farafonova T.N., Medvedev O.S., Kalenikova E.I., Korotaeva A.L. Vozmozhnosti primeneniya razlichny`x doz koe`nzima Q10 u bol`ny`x xronicheskoj serdechnoj nedostatochnost`yu. Zhurnal Serdechnaya Nedostatochnost`. 2010;11 (4):218–23].
43. Токарева О.Г., Харитонова Е.В., Мареев В.Ю., Каленикова Е.И., Медведев О.С. Влияние коэнзима Q10 в составе стандартной терапии больных хронической сердечной недостаточностью на плазменные уровни мозгового натрийуретического пептида. Журнал Сердечная Недостаточность. 2014;85(4):232–7 [Tokareva O.G., Xaritonova E.V., Mareev V.Yu., Kalenikova E.I., Medvedev O.S. Vliyanie koe`nzima Q10 v sostave standartnoj terapii bol`ny`x xronicheskoj serdechnoj nedostatochnost`yu na plazmenny`e urovni mozgovogo natrijureticheskogo peptida. Zhurnal Serdechnaya Nedostatochnost`. 2014;85 (4):232–7].
44. Berman M, Erman A, Ben-Gal T, Dvir D, Georghiou G, Stamler A et al. Coenzyme Q10 in patients with end-stage heart failure awaiting cardiac transplantation: a randomized, placebo-controlled study. Clin Cardiol. 2004 May;27(5):295-9.
45. Alehagen U, Johansson P, Bjornstedt M, Rosen A, Dahlstrom U. Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: a 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens. Int J Cardiol. 2013 Sep 1;167(5):1860-6.
46. Mortensen SA, Rosenfeldt F, Kumar A, Dolliner P, Filipiak KJ, Pella D et al. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. JACC Heart Fail. 2014 Dec;2(6):641–9.
47. DiNicolantonio JJ, Bhutani J, McCarty MF, O'Keefe JH. Coenzyme Q10 for the treatment of heart failure: a review of the literature. Open Heart. 2015 Oct 19;2(1):e000326.
48. Mortensen SA. Coenzyme Q10: will this natural substance become a guideline-directed adjunctive therapy in heart failure? JACC Heart Fail. 2015 Mar;3(3):270-1.
Mareev V.Yu., Minina Yu.V., Begrambekova Yu.L. KUDESan® (3% drops for oral use) in treatment of patieNts with heart failure: efficacy and safety In Combination with standard therapy (KUDESNIC). Design and results of a prospective, randomized, double-blind KUDESNIC study. Russian Heart Failure Journal. 2016;17 (4):236–249

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