CC BY
13
Резюме. Целью исследования было повышение эффективности лечения пациентов с НАСГ и ГСГХ путем комплексного обследования и разработки персонифицированной гиполипидемической терапии. Объект и методы. Проведено комплексное обследование 73 (n = 73) больных и выделены группы пациентов: I - получала терапию розувастатином 20 мг/сут (n = 17); II - розувастатин 20 мг/сут и омега-3 ПНЖК «Эпадол-нео» (n = 27); III - розувастатин 20 мг/сут и гепатопротектор «Гепадиф» (n = 29); контрольную группу составили практически здоровые лица (n = 10). Оценку эффективности проводили на 45-ые и 90-ые сутки терапии путем клинических, лабораторно-инструментальных методов исследований.
Результаты. Гиполипидемическая терапия, с добавлением гепатопротектора «Гепадиф», достоверно приводила к достижению целевых уровней ЛПНП (р = 0,001) уменьшению активности печеночных ферментов - АЛТ на 66%, АСТ на 46% (р = 0,001) и сопровождалась снижением выраженности астенического, диспеп-тического синдромов, снижением эхогенности, ткани печени по данным УЗИ, что позволяет считать данное лечение терапией выбора у пациентов с НАСГ и ГСГХ.
Ключевые слова: дислипидемия, неалкогольный стеатогепатит, гетерозиготная семейная гиперхолесте-ринемия, омега-3 полиненасыщенные жирные кислоты, гепатопротектор.
COMPLEX HYPOLIPIDEMIC THERAPY OF PATIENTS WITH NON-ALCOHOLIC STEATOHEPATITIS AND FAMILIAL HYPERCHOLESTEREMIA
Yakimenko O., Maznichenko Ie.
Abstract. Hypercholesterolemia is a major risk factor for the development of CVD and NASH, the presence of such comorbid pathology contributes to the early manifestation of cardiovascular accidents. The aim of the study was to increase the effectiveness of treatment of NASH with HHC through a comprehensive examination of patients and the development of personalized lipid-lowering therapy. Object and methods. A comprehensive examination of 73 (n = 73) patients was carried out and groups of patients matched by age and sex were selected: I - received therapy with rosuvastatin 20 mg/day (n = 17); II - rosuvastatin 20 mg/day and omega-3 PUFA "Epadol-neo" (n = 27); III - rosuvastatin 20 mg/day and hepatoprotector "Gepadif" (n = 29); the control group consisted of practically healthy individuals (n = 10). Evaluation of the effectiveness was carried out on the 45th and 90th days of therapy by clinical, laboratory and instrumental methods of investigation.
Results. In the first group, the AC level decreased by 29% (p = 0.037), but did not reach the target levels, the activity of hepatic enzymes was 40% higher than reference indices (p = 0.023). In II, AC decreased by 33% (p = 0.013) compared with the initial data, the activity of liver enzymes remained higher than the reference values. In the third group, a significant decrease in the level of LDL by 65% (p = 0.0001), an increase in HDL by 50%, a decrease in the activity of hepatic transaminases and echogenicity of the liver tissue, according to an ultrasound scan, was found. Findings. Comprehensive lipid-lowering therapy, with the addition of the hepatoprotector Gepadif, reliably led to the achievement of target LDL levels (p = 0.001) and decreased liver enzyme activity - ALT by 66%, AST by 46% (p = 0.001) and was accompanied by a decrease in asthenic, dyspeptic syndromes, a decrease in echogenicity, liver tissue according to ultrasound data, which makes it possible to consider this treatment as the therapy of choice in patients with NASH with GHSS.
Key words: dyslipidemia, nonalcoholic steatohepatitis, heterozygous familial hypercholesterolemia, omega-3 polyunsaturated fatty acids, hepatoprotector.
Рецензент - проф. Скрипник I. М.
Стаття наджшла 28.02.2019 року
DOI 10.29254/2077-4214-2019-1-2-149-211-215 UDC 615.036
Yakovleva О. О., Semenchuk S. A.
A COMPARATIVE ANALYSIS OF THE THERAPUTICAL EFFICACY OF L-ARGININE L-GLUTAMATE AND THIOTRIAZOLIN IN THE COMPLEX PHARMACOTHERAPY OF STABLE ISCHEMIC HEART DISEASE National Pirogov Memorial Medical University (Vinnytsia)
semenchuksvetlana1989@gmail.com
Publication relation to planned scientific research projects. The present paper is an integral part of the research study "Organ protective efficacy and safety of metabolic correctors in the treatment of comorbid pathological conditions", state registration № 0114U000195.
Introduction. Despite the developed approaches to the given patients treatment, ischemic heart disease (IHD) progression prevention, the main disease treatment ensuring and prognosis assessment are not always as much as possible effective. It is known that the conventional pharmacotherapy of IHD has been addressed from the perspective of cardiac hemodynamics improvement that is effective in preventing angina attacks but provide virtually no influence against pathogenetic links of the disease. That is why, the metabolic
therapy has rightfully taken its leading place among the treatment plans for cardiovascular disease and has been included in the international guidelines.
It is known that atherogenic dyslipidemia [1-3], endothelial dysfunction [4-5], chronic systemic inflammation [6-7] and hemodynamic disorders [8-10] play key role in pathogenesis of IHD.
L-arginine L-glutamate [11-13] is one of the patho-genetic-acting national metabolic drugs. The presence of L-arginine, a source of nitric oxide [14-15], restores endothelium-dependent vasodilation [16] and glutamic acid, as the precursor of glutathione peroxidase and glutathione transferase [17], regulates lipid peroxidation processes in the body [18]. At the same time, the analysis of literature data suggests that L-arginine L-glu-
Table 1.
Demographic and clinical characteristics of the patients between the study groups
Parameter, units of measurement ST n=48 LL n=50 T n=44
Men, n (%) 33 (68) 35 (71) 33(75)
Women, n (%) 16(32) 15 (29) 11(25)
Age, years 60,6±4,2 61,2±3,1 61,7±3,1
BMI, kg/m2 34.8±2.1 32.6±3.1 33,4±2.9
Mean duration of IHD, years 34.8±2.1 32.6±3.1 33,4±2.9
Previous MI, n (%) 48(100) 50(100) 44(100)
Hypertension, n (%) 31(65) 30(59) 27(61)
Use of statins, n (%) 48(100) 50(100) 44(100)
Use of antiplatelets, n (%) 48(100) 50(100) 44(100)
Use of beta-blockers, n (%) 48(100) 50(100) 44(100)
Use of ACE inhibitors, n (%) 37(87) 42(84) 38(86)
Use of angiotensin receptor blockers, n| (%) 11(13) 8(16) 6(14)
Use of calcium channel blockers, n (%) 12(25) 15(30) 10(23)
Abbreviation: ST=standard IHD therapy; LL=L-arginine L-glutamate; T=thiotriazolin.
tamate has not been studied in the aspect of treatment of coronary artery disease, despite its pathogenetic potential.
The main objective of this study was to compare effectiveness of L-arginine L-glutamate and thiotriazolin in the complex pharmacotherapy of stable ischemic heart disease.
Object and methods. A prospective, randomized, open label study was conducted on the basis of the rehabilitation department of "Khmilnyk" clinical sanatorium in Vinnytsia region during 2014-2017. In accordance with the objectives of the study, 142 subjects with stable IHD were screened.
Basic demographic and clinical characteristics of the patients are shown in table 1.
After the previous randomization and correction of outpatient treatment, patients were assigned three treatment options, depending on which the main clinical groups of the study were formed: the first clinical group consisted of 44 patients who received only optimal IHD therapy, the second group - 50 patients who received L-arginine L-glutamate in the complex pharmacotherapy, the third group consisted of 48 patients who received the drug - thiotriazolin in addition to standard treatment regimen. During the first 7 days, L-arginine L-glutamate (Glutargin, LLC "Zdorovya", Ukraine) was used parenterally - intravenously, drip into 5 ml of 40% solution of 200 ml of isotonic sodium chloride solu-
tion with the transition to a tablet form 0,75 g three times a day for 3 weeks. During the first 7 days, Tiotriazolin [19]. (Halychpharm, Ukraine) was used parenterally - intramuscularly for 2 ml of 2.5% solution twice a day with the transition to a tablet form in a dose of 200 mg three times a day for 3 weeks. The protocol of examination of patients and conditions of research were approved by the Committee on Bioethics by Vinnytsia National Pirogov Memorial Medical University (protocol number 6 dated September 6, 2018). All patients gave written consent to participate in the study and use the received data. The statistical analysis was carried out using the Statistica 6.0 statistical software package (data are presented as M±m); the differences were considered significant at p<0,05.
The evaluation of the treatment efficacy criteria was based on the reduction in the
Fig. 1. Reduction in the daily number of angina attacks in patients with stable IHD in 3 groups of treatment in %. Notes: ST=standard IHD therapy; LL=L-arginine L-glutamate; T=thiotriazolin; *-p<0,05.
Fig. 2. Reduction in the daily number of nitroglycerin tablets taken
by patients with stable IHD in 3 groups of treatment in %. Notes: ST=standard IHD therapy; LL=L-arginine L-glutamate; T=thiotriazolin; *-p<0,05.
number of painful and painless myocardial ischemia episodes and the total duration of episodes of ischemia per day according to 24-hour ECG monitoring data and the normalization of lipid blood profile.
Results. Addition of L-arginine L-glutamate or thiotri-azolin to the complex pharmacotherapy of patients with stable coronary artery disease induced a similar pattern in improvement of clinical course of IHD: reduction in the mean daily number of typical angina attacks and the mean number of nitroglycerin tablets (fig. 1, fig. 2).
The analysis of the evolution of the results of 24hour ECG monitoring over time revealed a reductions in the total duration of ischemia episodes by 29 % from 27,2±2,9 to 19,4±1,8 (p<0,05) in the group of patients with stable IHD treated with standard therapy; by 41 % from 28,3±2,6 to 16,7±1,5 (p<0,05) in the L-arginine L-glutamate group and by 38 % from 30,4±1,9 to 18,7±1,5 (p<0,05) in Thiotriazolin group.
As a result of treatment, patients with stable IHD were characterized by significant reduction of the number of supraventricular and ventricular extrasystoles of average gradation (II-III classes on B. Lown) in all groups of the study, statistically significant in 2 and 3 groups (by (-54,3 %) from 67,6±11,8 to 30,9±6,4 (p<0,05) and (-45,7 %) from 59,7±9,8 to 31,7±5,2 (p<0,05)). The antiarrhythmic effect of L-arginine L-glutamate is atrial cyclic guanosine monophosphate-related, which plays a key role in the functioning of the cardiac autonomic nervous system, restoring the sympathetic and parasympathetic balance, due to the vagal component [20].
The tendency to improve the structural and functional state of myocardium in the three study groups was revealed: the mean values of EDV in the group 2 decreased statistically significantly by 12,5 % (178,3±5,91 versus 156,1±7,42 ml (p<0,05)) and by 11,9 % (169,8±6,14 versus 149,5±5,37 ml (p<0,05) in group 3; ESV decreased by 19,3% (78,2±3,44 versus 63,1±2,42 ml (p<0,05)) and 18,1 % (75,41±3,17 versus 61,7±2,65 ml (p<0,05) respectively, which resulted in improvement of systolic function of the left ventricle, increase in EF, in group 2 was 6,7 % (56,8±2,9 versus 60,6±1,45 (p<0,05)) and 5,7 % (54,2±1,92 versus 57,3±1,28 (p<0,05)) in group 3.
The analysis of the obtained results showed superiority of the L-arginine L-glutamate to improve functional and structural state of liver and lipid levels in the patients with stable IHD (table 2).
Table 2.
Liver laboratory values and lipids' levels before and after therapy in study groups
Parameter, units LL (n=50) T (n=44)
Visit 1 Visit 2 Visit 1 Visit 2
AST, Mm/l 0,51±0,08 0,29±0,06* 0,56±0,09 0,40±0,06*
ALT, Mm/l 0,66±0,13 0,34±0,11* 0,73±0,12 0,50±0,09*
GGP, U/l 61,5±3,3 33,4±2,9* 63,8±4,5 29,6±3,1*
TBL, Mm/l 19,06±1,03 14,04±1,3* 20,05±2,02 18,75±1,18
TC, Mm/l 6,90±0,19 4,8±0,14* 6,56±0,22 5,21±0,19
TG 4,46±0,19 2,37±0,21* 4,16±0,22 3,03±0,17*
LDL-C 4.03±0.24 2.59±0.22* 3.73±0.19 2.99±0.21*
HDC-C 0,84±0,06 1,05±0,05* 0,93±0,08 1,06±0,17*
Abbreviation: LL: L-arginine L-glutamate; T: thiotriazolin; *-p<0,05 AST: Aspartate aminotransferase; ALT: Alanine aminotransferase GGT: Gamma-glutamyl transpeptidase; TBL: total bilirubin; TC total cholesterol; TG: triglycerides; LDL-C: Low-Density Lipoprotein Cholesterol; HDC-C: High-Density Lipoprotein Cholesterol.
Hepatobiliary symptoms in patients with stable IHD have been observed in 100 % of cases. Echoscopic signs of steatohepatosis: hepatomegaly was detected in 69 % of patients, hyperechogenicity of parenchyma - 63 %, complication of vascular visualization - 59 %, enlargement of the diameter of the portal vein - 27 %, and manifestations of cytolytic and cholestatic syndromes in more than half of the patients (52 % of patients showed a significant increase in alanine and 46 % in asparagine transaminase. The normal level of GGP was noted in 31 % of patients, the level of total bilirubin exceeded the reference in 24 % of cases.
The evaluation of the functional state of the liver in patients with stable IHD in the study groups showed superiority of the L-arginine L-glutamate group to decrease in cytolytic and cholestatic syndromes: reduction of ALT in group 2 was by 48,5 % (p<0,05), while in group 3 - by 31,1 % (p<0,05); the level of AST decreased by 43,1 % (p<0,05) and 28.6 % (0,05); the level of GGP decreased in group 2 and 3 by 45,7% (p<0.05) and 29.6% (p <0,05) respectively.
References
An analysis of changes in the lipid blood profile in various pharmacotherapy variants demonstrated lipid-correcting properties of both metabolically active drugs, but inclusion of L-arginine L-glutamate to the complex pharmacotherapy provided a better result compared with thiotriazolin. Thus, the level of TC in patients of the 2nd group decreased by - 30,4 % (p<0,05), while in patients of group 3 - by 20,5 % (p<0,05). The mean TG level decreased by 46,8 % (p<0,05) and 27,1 % (p<0,05) respectively. Target levels of LDL-C were achieved in the 1st group in 41 % cases, in the 2nd group - in 61 % of patients and in group 3 - 49 %, (p<0,05). The level of HDL-C in patients of group 2 increased by 25,0 % (p<0,05), while in group 2 - by 11,2 % (p<0,05).
The present study found that in the patients with stable IHD the favorable evolution of ultrasound symptoms, which characterize the structural state of the liver was observed only in 2 and 3 groups. The statistically significant prevalence of these indicators included in the optimal therapy of IHD L-arginine L-glutamate. Thus, the size of the liver in group 2 was normal in 35 % of patients (p<0,05), while in group 3 this percentage was only 19 % (p<0,05), the structure of the liver was restored in 37 % and 21 % of patients respectively, p<0,05. Improvement of the echogenicity of the liver parenchyma was recorded in 41 % of the 2 groups of patients treated with L-arginine L-glutamate and 26 % in group 3, p<0,05.
The absence of adverse changes in laboratory values indicates the safety of treatment with the study drug.
The therapeutic efficacy of L-arginine L-glutamate is confirmed by the WHO key criterion - the dynamics of life quality indices (statistically significant improvement in the state of health of the patients on the MacNew questionnaire was 8,2 %, p<0,05, the increase in physical activity, which reflects the decrease constraints for daily activities and positively affects the success of the recommended treatment, amounted to 23,2 %, p<0,05, an increase in social contacts and the level of communication occurred at 26,7 %, p<0,05).
Conclusions. A comparative analysis of the metabolic activity of L-arginine L-glutamate and the preparation of comparison of thiotriazolin in patients with stable IHD showed superiority of the first to improve hepatobiliary symptoms, while the level of anti-ischemic activity of both metabolic correctors did not differ statistically significantly.
Perspectives of further developments. In the future, it is planned to conduct further studies with the extension of the observation period for patients with stable IHD who additionally receive L-arginine L-glutamate.
Acknowledgments. I would like to acknowledge the help of Stotskaya Tamara in obtaining patient follow up.
Funding. There was no outside funding for this research.
Akin L, Kurtoglu S, Yikilmaz A, Kendirci M, Elmali F, Mazicioglu M. Fatty liver is a good indicator of subclinical atherosclerosis risk in obese children and adolescents regardless of liver enzyme elevation. Acta Paediatr. 2013;102(3):107-13. DOI: 10.1111/apa.12099 Ampuero J, Gallego-Durán R, Romero-Gómez M. Association of NAFLD with subclinical atherosclerosis and coronary-artery disease: metaanalysis. Rev Esp Enferm Dig. 2015;107(1):10-6.
Kucukazman M, Ata N, Yavuz B, Dal K, Sen O, Deveci OS, et al. Evaluation of early atherosclerosis markers in patients with nonalcoholic fatty liver disease. European journal of gastroenterology & hepatology. 2013;25(2):147-51. Available from: https://doi.org/10.1097/ meg.0b013e32835a58b1
Shukla V, Fatima J, Chaudhary S, Ali M, Mishra I. A Study of Endothelial Dysfunction in Patients of Non-Alcoholic Fatty Liver Disease. Journal of The Association of Physicians of India. 2017;65:18.
5. Tabit CE, Chung WB, Hamburg NM, Vita JA. Endothelial dysfunction in diabetes mellitus: Molecular mechanisms and clinical implications. Reviews in Endocrine and Metabolic Disorders. 2010;11(1):61-74. DOI: 10.1007/s11154-010-9134-4
6. Teague HL, Ahlman MA, Alavi A, Wagner DD, Lichtman AH, Nahrendorf M, et al. Unraveling Vascular Inflammation. Journal of the American College of Cardiology. 2017;70(11):1403-12. DOI: 10.1016/j.jacc.2017.07.750
7. Tousoulis D, Antoniades C, Stefanadis C. Assessing inflammatory status in cardiovascular disease. Heart. 2007;93(8):1001-7. DOI: 10.1136/ hrt.2006.088211
8. Zeikidze S. Diagnostic value of moderate dilatation of the left ventricle in asymptomic (silent) ischemia. Georgian medical news. 2017;271:66-70.
9. Simon TG, Bamira DG, Chung RT, Weiner RB, Corey KE. Nonalcoholic Steatohepatitis is Associated with Cardiac Remodeling and Dysfunction. Obesity. 2017;25(8):1313-6. DOI: 10.1002/oby.21879
10. Pandey A, Omar W, Ayers C, LaMonte M, Klein L, Allen NB, et al. Sex and Race Differences in Lifetime Risk of Heart Failure with Preserved Ejection Fraction and Heart Failure with Reduced Ejection Fraction. Circulation. 2018;137(17):1814-23. Available from: https://doi. org/10.1161/circulationaha.117.031622
11. Babak OYa, Frolov VM, Kharchenko NV. Glutargin-farmakologicheskoye deystviye i klinicheskoye primeneniye. Kharkov: Elton-2; 2005. 456 s. [in Russian].
12. Hlutarhin - instruktsiya dlya klinichnoho zastosuvannya preparatu. Zatverdzheno nakazom Ministerstva okhorony zdorov'ya Ukrayiny № 323 vid 05.06.2015. [in Ukrainian].
13. Xuan C, Tian QW, Li H, Zhang BB, He GW, Lun LM. Levels of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, and risk of coronary artery disease: A meta-analysis based on 4713 participants. European journal of preventive cardiology. 2016;23(5):502-10.
14. Lymanets TV, Maslova GS, Skrypnyk IM. The nitric oxide system imbalance role in the development of anthracycline cardiotoxicity in acute leukemia patients with concomitant ischemic heart disease. World of Medicine and Biology. 2016;12(57):035-040.
15. Dogru T, Genc H, Tapan S, Ercin CN, Ors F, Aslan F, et al. Elevated asymmetric dimethylarginine in plasma: an early marker for endothelial dysfunction in non-alcoholic fatty liver disease? Diabetes research and clinical practice. 2012;96(1):47-52.
16. Lee CW, Li D, Channon KM, Paterson DJ. L-arginine supplementation reduces cardiac noradrenergic neurotransmission in spontaneously hypertensive rats. Journal of molecular and cellular cardiology. 2009;47(1):149-55.
17. Zhang JX, Wang ZM, Zhang JJ, Zhu LL, Gao XF, Chen SL. Association of glutathione peroxidase-1 (GPx-1) rs1050450 Pro198Leu and Pro197Leu polymorphisms with cardiovascular risk: a meta-analysis of observational studies. J Geriatr Cardiol. 2014;11(2):141-50. DOI: 10.3969/j. issn.1671-5411.2014.02.003
18. Zhang S, Zhang S, Wang H, Wu W, Ye Y. Arginine methylation dysfunction increased risk of acute coronary syndrome in coronary artery disease population: A case-control study. Medicine (Baltimore). 2017;96(7):e6074. DOI: 10.1097/MD.0000000000006074
19. Tiotryazolin - instruktsiya dlya klinichnoho zastosuvannya. Zatverdzheno nakazom Ministerstva okhorony zdorov'ya Ukrayiny № 905 vid 15.12.2011. [in Ukrainian].
20. Stavrakis S, Scherlag BJ, Fan Y, Liu Y, Mao J, Varma V, et al. Inhibition of atrial fibrillation by low-level vagus nerve stimulation: the role of the nitric oxide signaling pathway. Journal of Interventional Cardiac Electrophysiology. 2013;36(3):199-208.
ПОР1ВНЯЛЬНИЙ АНАЛ1З ТЕРАПЕВТИЧНО1 ЕФЕКТИВНОСТ1 L-АРПНШУ, L-ГЛУТАМАТУ ТА Т1ОТРИАЗОЛ1НУ В КОМПЛЕКСН1Й ФАРМАКОТЕРАПП СТАБ1ЛЬНОТ 1ШЕМ1ЧНО1 ХВОРОБИ СЕРЦЯ Яковлева О. О., Семенчук С. А.
Резюме. Оптимальна фармакотератя ше1^чноТ хвороби (1ХС) серця розглядаеться з точки зору полтшення серцевоТ гемодинамти, яка ефективна у запоб^анш анпнозних нaпaдiв, але практично не впливае на патогенетичш ланки захворювання. Тому метaболiчнa тератя по праву зайняла провщне мкце в рекомендащях по лтуванню серцево-судинних захворювань i включена в мiжнaроднi рекомендаций Метою дослщження було порiвняти ефектившсть L-арпншу L-глутамату та тютриазолшу в комплекснш фармакотерапп стабшьноТ 1ХС. У вщповщносл до завдань дослщження було обстежено 142 особи iз стабтьною 1ХС. Пкля попередньоТ рaндомiзaцiТ i корекцп амбулаторного лтування патентам було призначено три вaрiaнти терапп, залежно вщ якоТ i формувались основы клЫчш групи дослщження: 1 групу склали 44 пащенти, як отриму-вали лише оптимальну тератю 1ХС, 2 групу — 50 хворих, ям отримували L-арпнш L-глутамат в комплекснш фармакотерапп, 3 групу — 48 хворих, ям отримували препарат-тютриазолш на додаток до стандартно! схеми лтування. Оцшка функцюнального стану печшки у пащенлв зi стабтьною 1ХС в дослщжуваних групах показала перевагу групи з L-арпншом L-глутамат щодо зниження цитолп"ичного i холестатичного синдромiв: зниження АЛТ в 2-й грут було на 48,5 % (р<0,05), а в грут 3 - на 31,1 % (р<0,05); рiвень АСТ знизився на 43,1 % (р<0,05) i 28,6 %; рiвень ГГТП знизився в 2 i 3 групи на 45,7 % (р<0,05) i 29,6 % вiдповiдно. Рiвень ЗХ у пащенлв 2-Т групи знизився на 30,4 % (р<0,05), а у пащенлв 3-Т групи - на 20,5 %. Середнш рiвень ТГ знизився на 46,8 % (р<0,05) i 27,1 % (р<0,05) вiдповiдно. Цiльовi рiвнi ЛПНЩ були досягнул в 1-й грут в 41 % випадмв, в 2-й грут - у 61 % пащенлв i в 3-й груш - 49 %, (р<0,05). Рiвень ЛПВЩ у пaцiентiв 2-Т групи збшьшився на 25,0 % (р<0,05), а у 2-й групi - на 11,2 %. Антиiшемiчний ефект двох метaболiчних препaрaтiв був пщтверджений 24-годинним монiторингом ЕКГ, але статистично не вiдрiзнявся.
Ключовi слова: iшемiчнa хвороба серця, L-aргiнiн L-глутамат, тютриазолш, печiнкa.
СРАВНИТЕЛЬНЫЙ АНАЛИЗ ТЕРАПЕВТИЧЕСКОЙ ЭФФЕКТИВНОСТИ L-АРГИНИНА L-ГЛУТАМАТА И ТИОТРИА-ЗОЛИНА В КОМПЛЕКСНОЙ ФАРМАКОТЕРАПИИ СТАБИЛЬНОЙ ИШЕМИЧЕСКОЙ БОЛЕЗНИ СЕРДЦА Яковлева О. А., Семенчук С. А.
Резюме. Оптимальная фармакотерапия ишемической болезни сердца (ИБС) рассматривается с точки зрения улучшения сердечной гемодинамики, которая эффективна в предотвращении ангинозных приступов, но практически не влияет на патогенетические звенья заболевания. Поэтому метаболическая терапия по праву заняла ведущее место в рекомендациях по лечению сердечно-сосудистых заболеваний и включена в международные рекомендации. Целью исследования было сравнить эффективность L-аргинина L-глутамата и тио-триазолина в комплексной фармакотерапии стабильной ИБС. В соответствии с задачами исследования было обследовано 142 человека со стабильной ишемической болезнью сердца. После предварительной рандоми-
зации и коррекции амбулаторного лечения пациентам было назначено три варианта терапии, в зависимости от которой и формировались основные клинические группы исследования: 1 группу составили 44 пациентов, получавших только оптимальную терапию ИБС, 2 группу - 50 больных, получавших L-аргинин L- глутамат в комплексной фармакотерапии, 3 группу - 48 больных, получавших препарат-тиотриазолин в дополнение к стандартной схемы лечения. Оценка функционального состояния печени у пациентов со стабильной ИБС в исследуемых группах показала превосходство группы с L-аргинином L-глутаматом по снижению цитолитиче-ского и холестатического синдромов: снижение АЛТ во 2-й группе было на 48,5 % (р <0,05), а в группе 3 - на 31,1 % (р<0,05); уровень АСТ снизился на 43,1 % (р<0,05) и 28,6 %; уровень ГГТП снизился во 2 и 3 группе на 45,7 % (р<0,05) и 29,6 % соответственно. Уровень ОХ у пациентов 2-й группы снизился на - 30,4 % (р<0,05), а у пациентов 3-й группы - на 20,5 %. Средний уровень ТГ снизился на 46,8 % (р<0,05) и 27,1 % (р<0,05) соответственно. Целевые уровни ЛПНП были достигнуты в 1-й группе в 41 % случаев, во 2-й группе - в 61 % пациентов и в 3-й группе - 49 %, (р<0,05). Уровень ЛПВП у пациентов 2-й группы увеличился на 25,0 % (р<0,05), а во 2-й группе - на 11,2 %. Антиишемический эффект двух метаболических препаратов был подтвержден 24-часовым мониторингом ЭКГ, но статистически не различался.
Ключевые слова: ишемическая болезнь сердца, L-аргинин L-глутамат, тиотриазолин, печень.
A COMPARATIVE ANALYSIS OF THE THERAPUTICAL EFFICACY OF L-ARGININE L-GLUTAMATE AND THIOTRIAZO-LIN IN THE COMPLEX PHARMACOTHERAPY OF STABLE ISCHEMIC HEART DISEASE Yakovleva О. О., Semenchuk S. A.
Abstract. The optimal pharmacotherapy of ischemic heart disease (IHD) has been addressed from the perspective of cardiac hemodynamics improvement that is effective in preventing angina attacks but provide virtually no influence against pathogenetic links of the disease. That is why, the metabolic therapy has rightfully taken its leading place among the treatment plans for cardiovascular disease and has been included in the international guidelines. The purpose of the study was to compare effectiveness of L-arginine L-glutamate and thiotriazolin in the complex pharmacotherapy of stable IHD. In accordance with the objectives of the study, 142 subjects with stable IHD were screened. After the previous randomization and correction of outpatient treatment, patients were assigned three treatment options, depending on which the main clinical groups of the study were formed: the first clinical group consisted of 44 patients who received only optimal IHD therapy, the second group — 50 patients who received L-Arginine L-glutamate in the complex pharmacotherapy, the third group consisted of 48 patients who received the drug — thiotriazolin in addition to standart treatment regimen. The evaluation of the functional state of the liver in patients with stable IHD in the study groups showed superiority of the L-arginine L-glutamate group to decrease in cytolytic and cholestatic syndromes: reduction of ALT in group 2 was by 48,5 % (p<0,05), while in group 3 - by 31,1 % (p<0,05); the level of AST decreased by 43,1 % (p<0,05) and 28,6 %; the level of GGP decreased in group 2 and 3 by 45,7% (p<0,05) and 29,6% (p<0,05) respectively. The level of TC in patients of the 2nd group decreased by - 30,4 % (p<0,05), while in patients of group 3 - by 20,5 %. The mean TG level decreased by 46,8 % (p<0,05) and 27,1 % respectively. Target levels of LDL-C were achieved in the 1st group in 41 % cases, in the 2nd group - in 61 % of patients and in group 3 - 49 %, (p<0,05). The level of HDL-C in patients of group 2 increased by 25,0 % (p<0,05), while in group 2 - by 11,2 %(p<0,05). The anti-ischemic effect of both metabolic drugs was confirmed with 24-hour ECG monitoring, but did not statistically differ.
Key words: ischemic heart disease, L-arginine L-glutamate, thiotriozolin, liver.
Рецензент - проф. Катеренчук I. П.
Стаття наджшла 27.03.2019 року
DOI 10.29254/2077-4214-2019-1-2-149-215-220
УДК 616.12-008.331.1-005.4-008.315-036.1:616.125-008.313-037:616.15-07 Яловенко М. I., Ханюков О. О.
ПРОГНОСТИЧНЕ ЗНАЧЕННЯ ПОКАЗНИК1В ВИСОКОЧУТЛИВОГО С-РЕАКТИВНОГО Б1ЛКА ПЛАЗМИ
КРОВ1 ТА СИСТЕМИ ЦИТОК1Н1В ДЛЯ ОЦ1НКИ РИЗИКУ РОЗВИТКУ Ф1БРИЛЯЦП ПЕРЕДСЕРДЬ У ПАЦ16НТ1В З АРТЕР1АЛЬНОЮ ППЕРТЕНЗ16Ю, 1ШЕМ1ЧНОЮ ХВОРОБОЮ СЕРЦЯ ТА ХРОН1ЧНОЮ
СЕРЦЕВОЮ НЕДОСТАТН1СТЮ Державний заклад «Дншропетровська медична академ1я МЫстерства охорони здоров'я УкраТни» (м. Дншро)
Y.marusia@gmail.com
Зв'язок публшацм з плановими науково-дослщ-ними роботами. Дослщження проведено в рамках науково-дослщноТ теми кафедри «Особливост струк-турно-функцюнальних змш серцево-судинноТ систе-ми у хворих на артер1альну ппертензш, шем1чну хворобу серця в поеднаш з коморбщними станами», № державноТ реестрацп 0117u004729, термш виконання 01.2017-12.2020.
Вступ. Ф1бриляц1я передсердь (ФП) е найпошире-шшою аритм1ею у клЫчнш практик, що пов'язана ¡з зростанням швалщносп i смертность Кшьшсть хво-
рих продовжуе неспинно зростати та на даний час становить 3% населення европейськоТ популяцп [1]. Поширення ФП пов'язують не тшьки зi збшьшенням середнього вту населення, а й з коморбщшстю захво-рювань та розповсюджешстю фам^в ризику (ФР). У 2/3 пащенлв виразшсть симптоматики, що пов'язана з ФП, значно впливае на яшсть життя та призводить до збшьшення ктькосп госпiталiзацiй, проте у 1/3 ви-падшв переб^ ФП мае безсимптомний характер, що ускладнюе своечасну дiагностику та початок лтуван-ня [2].
