Controlling blood pressure and progression of hypertension-dependent cardiovascular continuum by amlodipine and perindopril A single pill fixed‑dose combination: focus on endothelial dysfunction and metabolic risks
https://doi.org/10.18705/1607-419X-2024-2435
EDN: RCPKHQ
Abstract
Due to its broad spectrum of pathogenic target points, fixed-dose combination therapy is considered a benchmark approach to successful treatment of arterial hypertension (HTN) and HTN-associated cardiovascular conditions. This results from endothelium insufficiency of various origin, so the use of combination of angiotensinconverting enzyme inhibitors and calcium channel blockers is an optimal treatment choice. The review highlights key points of single pill amlodipine and perindopril A combination use and its key position in modern concept of hypertension management. We have focused on the metabolic neutrality of fixed-dose amlodipine and perindopril A combination, its ability to delay rapid progression of already acquired metabolic changes. We briefly highlight fundamental observational and randomized studies, in particular, those regarding effectiveness of the drug components and its effect on the end points as a fixed-dose combination. The last but not least, we emphasize vasoand cardioprotective properties of the drug as well as its safety profile.
About the Authors
T. S. SveklinaRussian Federation
Tatiana S. Sveklina, MD, PhD, Associate Professor, Internal Diseases Propadeutics Department
Suvorovsky av., 63a, St Petersburg, 191124
A. N. Kuchmin
Russian Federation
Alexey N. Kuchmin, MD, PhD, DSc, Head and Professor, Department of Propedeutics of Internal Diseases
St Petersburg
V. V. Konyaev
Russian Federation
Vladislav V. Konyaev, the 6th Year Student
St Petersburg
P. D. Oktysyuk
Russian Federation
Polina D. Oktysyuk, the 6th Year Student
St Petersburg
A. I. Rechkalova
Russian Federation
Alina I. Rechkalova, the 6th Year Student
St Petersburg
References
1. Kobalava ZhD, Konradi AO, Nedogoda SV, Shlyakhto EV, Arutyunov GP, Baranova EI et al. Arterial hypertension in adults. Clinical guidelines 2020. Russian Journal of Cardiology. 2020;25(3):3786. doi:10.15829/1560-4071-2020-3-3786. In Russian.
2. Dat TV, Tu VL, Thu LNA, Quang NNA, Binh V, Nga NTQ et al. Effectiveness of perindopril/amlodipine fixed-dose combination in the treatment of hypertension: a systematic review. Front Pharmacol. 2024;14:1156655. doi:10.3389/fphar.2023.1156655
3. Gimbrone MA Jr, García-Cardeña G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res. 2016;118(4):620–636. doi:10.1161/CIRCRESAHA.115.306301
4. Malekmohammad K, Sewell RDE, Rafieian-Kopaei M. Antioxidants and atherosclerosis: mechanistic aspects. Biomolecules. 2019;9(8):301. doi:10.3390/biom9080301
5. Falk E. Pathogenesis of atherosclerosis. J Am Coll Cardiol. 2006;47(8 Suppl):C7-C12. doi:10.1016/j.jacc.2005.09.068
6. Singh S, Anshita D, Ravichandiran V. MCP 1: Function, regulation, and involvement in disease. Int Immunopharmacol. 2021;101(Pt B):107598. doi:10.1016/j.intimp.2021.107598
7. Higashi Y, Kihara Y, Noma K. Endothelial dysfunction and hypertension in aging. Hypertens Res. 2012;35(11):1039–1047. doi:10.1038/hr.2012.138
8. Li R, Mi X, Yang S, Yang Y, Zhang S, Hui R et al. Longterm stimulation of angiotensin II induced endothelial senescence and dysfunction. Exp Gerontol. 2019;119:212–220. doi:10.1016/j.exger.2019.02.012
9. Konukoglu D, Uzun H. Endothelial dysfunction and hypertension. Adv Exp Med Biol. 2017;956:511–540. doi:10.1007/5584_2016_90
10. Kelly AS, Gonzalez-Campoy JM, Rudser KD, Katz H, Metzig AM, Thalin M et al. Carvedilol-lisinopril combination therapy and endothelial function in obese individuals with hypertension. J Clin Hypertens (Greenwich). 2012;14(2):85–91. doi:10.1111/j.1751-7176.2011.00569.x
11. Ferrari R. Optimizing the treatment of hypertension and stable coronary artery disease: clinical evidence for fixedcombination perindopril/amlodipine. Curr Med Res Opin. 2008;24(12):3543–3557. doi:10.1185/03007990802576302
12. Xu S, Ilyas I, Little PJ, Li H, Kamato D, Zheng X et al. Endothelial dysfunction in atherosclerotic cardiovascular diseases and beyond: from mechanism to pharmacotherapies. Pharmacol Rev. 2021;73(3):924–967. doi:10.1124/pharmrev.120.000096
13. Meng J, Xiao G, Zhang J, He X, Ou M, Bi J et al. Reninangiotensin system inhibitors improve the clinical outcomes of COVID 19 patients with hypertension. Emerg Microbes Infect. 2020;9(1):757–760. doi:10.1080/22221751.2020.1746200
14. Benincasa G, Coscioni E, Napoli C. Cardiovascular risk factors and molecular routes underlying endothelial dysfunction: Novel opportunities for primary prevention. Biochem Pharmacol. 2022;202:115108. doi:10.1016/j.bcp.2022.115108
15. Mouton AJ, Li X, Hall ME, Hall JE. Obesity, hypertension, and cardiac dysfunction novel roles of immunometabolism in macrophage activation and inflammation. Circ. Res. 2020;126:789– 806. doi:10.1161/CIRCRESAHA.119.312321
16. Mendoza MF, Kachur SM, Lavie CJ. Hypertension in obesity. Curr Opin Cardiol. 2020;35(4):389–396. doi:10.1097/HCO.0000000000000749
17. Boutens L, Stienstra R. Adipose tissue macrophages: going off track during obesity. Diabetologia. 2016;59(5):879–894. doi:10.1007/s00125-016-3904-9
18. Liu R, Nikolajczyk BS. Tissue immune cells fuel obesityassociated inflammation in adipose tissue and beyond. Front Immunol. 2019;10:1587. doi:10.3389/fimmu.2019.01587
19. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112(12):1821–1830. doi:10.1172/JCI19451
20. Crewe C, An YA, Scherer PE. The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. J Clin Invest. 2017;127(1):74–82. doi:10.1172/JCI88883
21. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res. 2005;46(11):2347–2355. doi:10.1194/jlr.M500294-JLR200
22. Wallace AM, McMahon AD, Packard CJ, Kelly A, Shepherd J, Gaw A et al. Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation. 2001;104(25):3052 3056. doi:10.1161/hc5001.101061
23. Koh KK, Park SM, Quon MJ. Leptin and cardiovascular disease: response to therapeutic interventions. Circulation. 2008;117(25):3238–3249. doi:10.1161/CIRCULATIONAHA.107.741645
24. Gritsenko OV, Chumakova GA, Gruzdeva OV, Shevlyakov IV. The relationship of epicardial obesity and levels of cardiac fibrosis markers. Russian Journal of Cardiology. 2019;(4):13–19. doi:10.15829/1560-4071-2019-4-13-19. In Russian.
25. Mellor KM, Bell JR, Ritchie RH, Delbridge LM. Myocardial insulin resistance, metabolic stress and autophagy in diabetes. Clin Exp Pharmacol Physiol. 2013;40(1):56–61. doi:10.1111/j.1440-1681.2012.05738.x
26. Li J, Solus J, Chen Q, Rho YH, Milne G, Stein CM et al. Role of inflammation and oxidative stress in atrial fibrillation. Heart Rhythm. 2010;7(4):438–444. doi:10.1016/j.hrthm.2009.12.009
27. Ishii Y, Abe I, Kira S, Harada T, Takano M, Oniki T et al. Detection of fibrotic remodeling of epicardial adipose tissue in patients with atrial fibrillation: Imaging approach based on histological observation. Heart Rhythm O2. 2021;2(4):311–323. doi:10.1016/j.hroo.2021.05.006
28. Poteshkina NG. Arterial hypertension and diabetes mellitus: a quest for optimal treatment — an experience of perindopril A/ amlodipine usage. Russian Journal of Cardiology. 2014;(12):64–70. doi:10.15829/1560-4071-2014-12-64-70. In Russian.
29. Gupta AK, Dahlof B, Dobson J, Sever PS, Wedel H, Poulter NR. Determinants of new-onset diabetes among 19,257 hypertensive patients randomized in the Anglo-Scandinavian Cardiac Outcomes Trial — Blood Pressure Lowering Arm and the relative influence of antihypertensive medication. Diabetes Care. 2008;31(5):982–988. doi:10.2337/dc07-1768
30. Marre M, Leye A. Effects of perindopril in hypertensive patients with or without type 2 diabetes mellitus, and with altered insulin sensitivity. Diab Vasc Dis Res. 2007;4(3):163–173. doi:10.3132/dvdr.2007.037
31. Wu HY, Huang JW, Lin HJ, Liao WC, Peng YS, Hung KY et al. Comparative effectiveness of renin-angiotensin system blockers and other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-analysis. Br Med J. 2013;347: f6008. doi:10.1136/bmj.f6008
32. Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet. 2007; 369(9557):201–207. doi:10.1016/S0140-6736(07)60108-1
33. Pitt B, Byington RP, Furberg CD, Hunninghake DB, Mancini GB, Miller ME et al. Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. PREVENT Investigators. Circulation. 2000;102(13):1503–1510. doi:10.1161/01.cir.102.13.1503
34. Nissen SE, Tuzcu EM, Libby P, Thompson PD, Ghali M, Garza D et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. JAMA. 2004;292(18):2217–2225. doi:10.1001/jama.292.18.2217
35. Werida R, Khairat I, Khedr L, El-Sisi AE. Comparative effects of enalapril versus perindopril on serum levels of leptin and adiponectin in hypertensive patients. Acta Cardiol. 2020;75(6):551– 556. doi:10.1080/00015385.2019.1636533
36. Bak JF, Gerdes LU, Sørensen NS, Pedersen O. Effects of perindopril on insulin sensitivity and plasma lipid profile in hypertensive non-insulin-dependent diabetic patients. Am J Med. 1992;92(4B):69S 72S. doi:10.1016/0002-9343(92)90151-z
37. Nedogoda SV, Ledyaeva AA, Chumachok EV, Tsoma VV, Mazina G, Salasyuk AS et al. Randomized trial of perindopril, enalapril, losartan and telmisartan in overweight or obese patients with hypertension. Clin Drug Investig. 2013;33(8):553–561. doi:10.1007/s40261-013-0094-9
38. Ueno S, Hamada T, Taniguchi S, Ohtani N, Miyazaki S, Mizuta E et al. Effect of antihypertensive drugs on uric acid metabolism in patients with hypertension: cross-sectional cohort study. Drug Res (Stuttg). 2016;66(12):628–632. doi:10.1055/s-0042-113183
39. Nádházi Z, Dézsi CA. The results of ACES (Antihypertensive Combinations’ Long Term Efficacy Comparing Study): analysis of metabolic effects of antihypertensive combination therapies. Clin Drug Investig. 2016;36(10):819–827. doi:10.1007/s40261-016-0431-x
40. Nagorny MB, Kuchmin AN. Review of 20 year results of ASCOT Legacy. Russian Journal of Cardiology. 2023;28(5):5457. doi:10.15829/1560-4071-2023-5457. In Russian.
Supplementary files
Review
For citations:
Sveklina T.S., Kuchmin A.N., Konyaev V.V., Oktysyuk P.D., Rechkalova A.I. Controlling blood pressure and progression of hypertension-dependent cardiovascular continuum by amlodipine and perindopril A single pill fixed‑dose combination: focus on endothelial dysfunction and metabolic risks. "Arterial’naya Gipertenziya" ("Arterial Hypertension"). 2024;30(2):224-231. (In Russ.) https://doi.org/10.18705/1607-419X-2024-2435. EDN: RCPKHQ