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Сравнительная оценка показателей артериальной жесткости и эндотелиальной дисфункции в динамике лечения фиксированными комбинациями антигипертензивных препаратов у пациентов с артериальной гипертензией и ишемической болезнью сердца
© ООО «КОНСИЛИУМ МЕДИКУМ», 2025 г.
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Khakuasheva IA, Umetov MA, Urusbieva DM, Abukova AKh, Didanova LA. Comparative assessment of arterial stiffness and endothelial dysfunction during treatment with fixed combinations of antihypertensive drugs in patients with arterial hypertension and coronary artery disease. Consilium Medicum. 2025;27(1):47–54. DOI: 10.26442/20751753.2025.1.203165
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Материалы и методы. В исследование вошли 52 пациента с неконтролируемой АГ с уровнем систолического артериального давления (САД)≥160 мм рт. ст. и/или диастолического АД (ДАД)≥90 мм рт. ст. в сочетании со стабильной стенокардией напряжения, принимавшие на момент начала исследования два антигипертензивных препарата. В зависимости от проводимого лечения участников разбили на 2 группы: группу 1 составили 27 человек, получавших ФК амлодипин/индапамид/периндоприл, группу 2 – 25 пациентов, принимавших ФК амлодипин/валсартан/ГХТЗ. Все пациенты также получали β-адреноблокатор бисопролол в дозировке 5–10 мг и антиагрегант в дозе 75–100 мг.
Результаты. Через 12 нед наблюдения по сравнению с исходным уровнем в группах 1 и 2 отмечено значимое снижение офисного АД: САД – на 34,50 и 32,03 мм рт. ст. (p<0,001 для обеих групп), со значимыми различиями между группами (p=0,045), ДАД – на 13,28 и 13,79 мм рт. ст. соответственно (р<0,001 для обеих групп), без значимых различий между группами (p=0,052). Частота сердечных сокращений снизилась в обеих группах до 69,00 уд./мин, в отсутствие межгрупповых различий (p=0,061). В группах 1 и 2 через 12 нед наблюдения по сравнению с исходными значениями отмечено значимое улучшение показателей артериальной ригидности: снижение САД в аорте – на 23,50 и 27,00 мм рт. ст. (p<0,001 для обеих групп), ДАД в аорте – на 17,50 и 20,00 мм рт. ст. (p<0,001 для обеих групп), пульсового давления в аорте – на 4,50 и 8,00 мм рт. ст. (p<0,001), индекса аугментации – на 9,00 и 10,00% (p<0,001 для обеих групп), скорости распространения пульсовой волны – на 2,51 и 1,97 м/с (p<0,001 для обеих групп), со значимыми различиями между группами (p=0,032), лодыжечно-плечевого индекса – на 0,01 и 0,02 (p<0,001 для обеих групп), сосудистого возраста – на 5,00 года (p=0,001) и 3,00 года (p=0,025) [p=0,025 для сравнения между группами], улучшение показателя функции эндотелия – на 24,5% (p=0,015) и 18,0% (p<0,001) [p=0,015 для сравнения между группами]. Число эпизодов ишемии значимо снизилось в обеих группах: в группе 1 – с 2,8±0,3 до 1,2±0,2 в неделю (p=0,021), в группе 2 – с 2,5±0,6 до 1,5±0,3 (p=0,018), без значимых различий между группами.
Заключение. Обе тройные ФК – амлодипин/индапамид/периндоприл и амлодипин/валсартан/ГХТЗ – эффективно снижали офисное АД, улучшали сосудистую жесткость и эндотелиальную функцию у пациентов с АГ и ишемической болезнью сердца. ФК амлодипин/индапамид/периндоприл обеспечивала более выраженное снижение офисного САД, скорости распространения пульсовой волны, показателя функции эндотелия и сосудистого возраста. Обе схемы лечения снижали частоту ишемических эпизодов, без значимых различий между группами.
Ключевые слова: эндотелиальная дисфункция, артериальная жесткость, артериальная гипертензия, ишемическая болезнь сердца, сосудистый возраст, объемная сфигмография, компьютерная фотоплетизмография
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Aim. To evaluate and compare the efficacy and safety of two triple fixed combinations (FC) of antihypertensive drugs, amlodipine/indapamide/perindopril and amlodipine/valsartan/hydrochlorothiazide (HCTZ), in managing the clinical course in patients with grade 2-3 hypertension and functional class II and III coronary artery disease.
Materials and methods. The study included 52 patients with uncontrolled hypertension with systolic blood pressure (SBP)≥160 mmHg and/or diastolic blood pressure (DBP)≥90 mmHg combined with stable effort angina who were taking two antihypertensive drugs at the beginning of the study. Depending on the treatment, the participants were divided into two groups: Group 1 included 27 subjects who received FC of amlodipine/indapamide/perindopril, and Group 2 included 25 subjects who received FC of amlodipine/valsartan/HCTZ. All patients also received β-blocker bisoprolol 5-10 mg and antiplatelet agent 75-100 mg.
Results. After 12 weeks of follow-up compared to baseline, there was a significant decrease in office BP in Groups 1 and 2: SBP by 34.50 and 32.03 mmHg (p<0.001 for both groups), with significant differences between the groups (p=0.045), DBP by 13.28 and 13.79 mmHg, respectively (p<0.001 for both groups), without significant differences between the groups (p=0.052). The heart rate decreased in both groups to 69.00 bpm, with no intergroup differences (p=0.061). In Groups 1 and 2, after 12 weeks of follow-up, arterial stiffness significantly improved compared to baseline: SBP in the aorta decreased by 23.50 and 27.00 mmHg (p<0.001 for both groups), DBP in the aorta decreased by 17.50 and 20.00 mmHg (p<0.001 for both groups), pulse pressure in the aorta decreased by 4.50 and 8.00 mmHg (p<0.001), augmentation index decreased by 9.00% and 10.00% (p<0.001 for both groups), pulse wave velocity decreased by 2.51 and 1.97 m/s (p<0.001 for both groups), with significant differences between groups (p=0.032), the ankle-brachial index decreased by 0.01 and 0.02 (p<0.001 for both groups), vascular age decreased by 5.00 years (p=0.001) and 3.00 years (p=0.025) [p=0.025 for comparison between groups], endothelial function improved by 24.5% (p=0.015) and 18.0% (p<0.001) [p=0.015 for comparison between groups]. The number of ischemia episodes significantly decreased in both groups: in Group 1 from 2.8±0.3 to 1.2±0.2 per week (p=0.021), in Group 2 from 2.5±0.6 to 1.5±0.3 (p=0.018), with no significant differences between the groups.
Conclusion. Both triple FCs – amlodipine/indapamide/perindopril and amlodipine/valsartan/HCTZ – effectively reduced office BP and improved vascular stiffness and endothelial function in patients with hypertension and coronary artery disease. FC of amlodipine/indapamide/perindopril provided a more pronounced reduction in office SBP, pulse wave velocity, and vascular age, as well as endothelial function improvement. Both regimens reduced the incidence of ischemic episodes, with no significant differences between the groups.
Keywords: endothelial dysfunction, arterial stiffness, arterial hypertension, coronary heart disease, vascular age, volume sphygmography, computer photoplethysmography
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1. Zdravookhranenie v Rossii. 2023. Federal'naia sluzhba gosudarstvennoi statistiki. Available at: https://www.gks.ru. Accessed: 10.11.2024 (in Russian).
2. Panchenko EP. New Possibilities in the Treatment of Patients With Stable Manifestations of Atherothrombosis. Kardiologiia. 2017;57(12):82-9 (in Russian). DOI:10.18087/cardio.2017.12.10060
3. Benetos A, Petrovic M, Strandberg T. Hypertension Management in Older and Frail Older Patients. Circ Res. 2019;124(7):1045-00. DOI:10.1161/CIRCRESAHA.118.313236
4. Zhou B, Perel P, Mensah GA, Ezzati M. Global epidemiology, health burden and effective interventions for elevated blood pressure and hypertension. Nat Rev Cardiol. 2021;18(11):785-802. DOI:10.1038/s41569-021-00559-8
5. Hassan AKM, Abd-El Rahman H, Mohsen K, Dimitry SR. Impact of in-hospital blood pressure variability on cardiovascular outcomes in patients with acute coronary syndrome. J Clin Hypertens (Greenwich). 2017;19(12):1252-29. DOI:10.1111/jch.13107
6. Balanova YuA, Drapkina OM, Kutsenko VA, et al. Hypertension in the Russian population during the COVID-19 pandemic: sex differences in prevalence, treatment and its effectiveness. Data from the ESSE-RF3 study. Cardiovascular Therapy and Prevention. 2023;22(8S):3785 (in Russian). DOI:10.15829/1728-8800-2023-3785
7. Mancia G, Kreutz R, Brunström M, et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens. 2023;41(12):1874-2071. DOI:10.1097/HJH.0000000000003480
8. McEvoy JW, McCarthy CP, Bruno RM, et al. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. Eur Heart J. 2024;45(38):3912-4018. DOI:10.1093/eurheartj/ehae178
9. Kobalava ZhD, Konradi AO, Nedogoda SV, et al. 2024 Clinical practice guidelines for Hypertension in adults. Russian Journal of Cardiology. 2024;29(9):6117 (in Russian). DOI:10.15829/1560-4071-2024-6117
10. Zaman MA, Awais N, Satnarine T, et al. Comparing Triple Combination Drug Therapy and Traditional Monotherapy for Better Survival in Patients With High-Risk Hypertension: A Systematic Review. Cureus. 2023;15(7):e41398. DOI:10.7759/cureus.41398
11. Arutyunov AG, Nozdrin AV, Shavgulidze KB, et al. Differences between passport and biological (actual) age in the population of Russian patients with arterial hypertension (analysis of the HYPERION registry). Terapevticheskii Arkhiv (Ter. Arkh.). 2018;90(4):21-8 (in Russian). DOI:10.26442/terarkh201890421-28
12. Ralapanawa U, Sivakanesan R. Epidemiology and the Magnitude of Coronary Artery Disease and Acute Coronary Syndrome: A Narrative Review. J Epidemiol Glob Health. 2021;11(2):169-77. DOI:10.2991/jegh.k.201217.001
13. Arutyunov GP, Tarlovskaya EI, Arutyunov AG, et al. Patients with Non-Obstructive CAD and Multifocal Atherosclerosis: A Subanalysis of the KAMMA Registry (Clinical Registry for the Study of Patients with Identified Multifocal Atherosclerosis in the Russian Federation and Eurasian Countries). Kardiologiia (Cardiology). 2024;64(8):13-23 (in Russian). DOI:10.18087/cardio.2024.8.n26
14. Vrints C, Andreotti F, Koskinas KC, et al. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J. 2024;45(36):3415-537. DOI:10.1093/eurheartj/ehae177
15. Ábrahám G, Dézsi CA. The Antihypertensive Efficacy of the Triple Fixed Combination of Perindopril, Indapamide, and Amlodipine: The Results of the PETRA Study. Adv Ther. 2017;34(7):1753-73. DOI:10.1007/s12325-017-0572-1
16. Burnier M, Bakris G, Williams B. Redefining diuretics use in hypertension: why sel ect a thiazide-like diuretic? J Hypertens. 2019;37(8):1574-56. DOI:10.1097/HJH.0000000000002088
17. Bubnova MA, Kryuchkova ON, Itskova EA, et al. Efficacy of perindopril/amlodipine and valsartan/amlodipine combinations in patients with a combination of arterial hypertension and chronic obstructive pulmonary disease. South Russian Journal of Therapeutic Practice. 2022;3(1):42-9 (in Russian). DOI:10.21886/2712-8156-2022-3-1-42-49
18. Zbyshevskaya E, Makeeva T, Erinchek V, Zheming W, et al. Antihypertensive efficacy of a strategy for switching fr om free combinations to a fixed triple combination as assessed by vascular stiffness parameters. Journal of Hypertension. 2023;41(Suppl. 3):p e121. DOI: 10.1097/01.hjh.0000939984.50105
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20. Shahin Y, Khan JA, Chetter I. Angiotensin converting enzyme inhibitors effect on arterial stiffness and wave reflections: a meta-analysis and meta-regression of randomised controlled trials. Atherosclerosis. 2012; 221(1): 18-33.
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ФГБОУ ВО «Кабардино-Балкарский государственный университет им. Х.М. Бербекова», Нальчик, Россия
*inara2333@yandex.ru
________________________________________________
Inara A. Khakuasheva*, Murat A. Umetov, Dzhanneta M. Urusbieva, Alena Kh. Abukova, Liana A. Didanova
Berbekov Kabardino-Balkarian State University, Nalchik, Russia
*inara2333@yandex.ru