Fixed-dose combination of indapamide and amlodipine in the treatment of isolated systolic hypertension: analysis of the ARBALET study
https://doi.org/10.15829/1560-4071-2025-6486
EDN: CNUCOE
Abstract
Aim. To evaluate the effectiveness of single-pill combination of indapamide/ amlodipine in outpatients over 55 years of age with uncontrolled isolated systolic hypertension (ISH) in a real-world practice.
Material and methods. Retrospective analysis of data from participants in the multicenter, open-label observational ARBALET study conducted in Russia among patients with grade 1-2 hypertension without prior antihypertensive therapy or blood pressure (BP) control while taking the medications. The efficacy of indapamide/ amlodipine combination was assessed by changes in office systolic BP (SBP) and the rate of achieving the target SBP level (<140 mm Hg) after 2 weeks, 1 month, and 3 months in four following age groups: 55-59 years, 60-69 years, 70-79 years, and ≥80 years.
Results. The ARBALET study enrolled 2217 patients, of whom 626 had ISH and were included in this additional analysis (mean age 66,1±7,8 years; 165 men (26,4%)). The target SBP <140 mm Hg was achieved in 43%, 75%, and 93% of patients after 2 weeks, 1 month, and 3 months, respectively. Compared with the baseline, SBP decreased by 18,8±10,5 mm Hg, 27,2±10,6 mm Hg, and 31,8±9,9 mm Hg after 2 weeks, 1 month, and 3 months, respectively. The decrease in SBP after 3 months compared with the baseline in the subgroups 55-60 years, 60-69 years, 70-79 years, and ≥80 years was 30,3±9,4 mm Hg, 32,4±9,7 mm Hg, 32,5±10,7, and 28,9±9,6 mm Hg, respectively.
Conclusion. Administration of indapamide/amlodipine combination is associated with a significant reduction in SBP and a high rate of target BP achievement in patients with ISH over 55 years of age in a real-world practice.
Keywords
isolated systolic hypertension,
combination antihypertensive therapy,
indapamide/amlodipine fixed-dose combination
Supporting agencies: The article was prepared with the support of the Servier company. Trial ID: ISRCTN40812831.
About the Authors
Zh. D. Kobalava
Peoples’ Friendship University of Russia
Russian Federation
Russian Federation
Moscow
E. A. Troitskaya
Peoples’ Friendship University of Russia
Moscow
References
1. 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 Russ.) doi: 10.15829/1560-4071-2024-6117.
2. 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.
3. Palatini P, Rosei EA, Avolio A, et al. Isolated systolic hypertension in the young: a position paper endorsed by the European Society of Hypertension. J Hypertens. 2018;36(6):122236. doi:10.1097/HJH.0000000000001726.
4. Yano Y, Stamler J, Garside DB, et al. Isolated systolic hypertension in young and middleaged adults and 31-year risk for cardiovascular mortality: the Chicago Heart Association Detection project in industry study. J Am Coll Cardiol. 2015;65:327-35. doi:10.1016/j.jacc.2014.10.060.
5. Kobalava ZhD, Shavarova EK, Chomova IA, et al. Fixed combination of amlodipine/ indapamide-retard in the treatment of uncontrolled hypertension in subjects over 55 years old. "Arterial’naya Gipertenziya" ("Arterial Hypertension"). 2018;24(5):586-95. (In Russ.) doi:10.18705/1607-419X-2018-24-5-586-595.
6. Vishnevsky A, Andreev E, Timonin S. Mortality from cardiovascular diseases and life expectancy in Russia. Demographic review, 2017;4(5):45-70. doi:10.17323/demreview.v4i5.8566.
7. Liu X, Rodriguez CJ, Wang K. Prevalence and trends of isolated systolic hypertension among untreated adults in the United States. J Am Soc Hypertens. 2015;9(3):197-205. doi:10.1016/j.jash.2015.01.002.
8. McEniery CM, Yasmin, Wallace S, et al.; ENIGMA Study Investigators. Increased stroke volume and aortic stiffness contribute to isolated systolic hypertension in young adults. Hypertension. 2005;46(1):221-6. doi:10.1161/01.HYP.0000165310.84801.e0.
9. O’Donnell CJ, Ridker PM, Glynn RJ, et al. Hypertension and borderline isolated systolic hypertension increase risks of cardiovascular disease and mortality in male physicians. Circulation. 1997;95(5):1132-7. doi:10.1161/01.cir.95.5.1132.
10. Yano Y. Blood Pressure in Young Adults and Cardiovascular Disease Later in Life. Am J Hypertens. 2021;34(3):250-7. doi:10.1093/ajh/hpab005. PMID: 33821946.
11. Atasoy S, Middeke M, Johar H, et al. Cardiovascular mortality risk in young adults with isolated systolic hypertension: findings from population-based MONICA/KORA cohort study. J Hum Hypertens. 2022;36(12):1059-65. doi:10.1038/s41371-021-00619-z.
12. Bae EH, Lim SY, Jung JH, et al. Chronic Kidney Disease Risk of Isolated Systolic or Diastolic Hypertension in Young Adults: A Nationwide Sample Based-Cohort Study. J Am Heart Assoc. 2021;10(7):e019764. doi:10.1161/JAHA.120.019764.
13. Scott H, Barton MJ, Johnston ANB. Isolated systolic hypertension in young males: a scoping review. Clin Hypertens. 2021;27(1):12. doi:10.1186/s40885-021-00169-z.
14. Eeftinck Schattenkerk DW, van Gorp J, Vogt L, et al. Isolated systolic hypertension of the young and its association with central blood pressure in a large multi-ethnic population. The HELIUS study. Eur J Prev Cardiol. 2018;25(13):1351-9. doi:10.1177/2047487318777430.
15. Kobalava ZD, Shavarova EK, Burtsev YP. Evaluation of the effectiveness of single-pill combination with indapamide and amlodipine in patients older 55 years in real-world practice in Russia (ARBALET study). J Hypertens. 2019;37:p e106. doi:10.1097/01.hjh.0000571372.74309.88.
16. Kobalava ZhD, Tolkacheva VV, Bagmanova NKh, Khasanova ER. Efficacy and tolerance of Arifam in patients with arterial hypertension over 55 years old: main results of the observational program ARBALET. Russian Journal of Cardiology. 2018;(12):64-74. (In Russ.) doi:10.15829/1560-4071-2018-12-64-74.
17. Unger T, Borghi C, Charchar F, et al. 2020 International Society of Hypertension global hypertension practice guidelines. J Hypertens. 2020;38(6):982-1004. doi:10.1097/HJH.0000000000002453.
18. Kim JH, Thiruvengadam R. Hypertension in an ageing population: Diagnosis, mechanisms, collateral health risks, treatments, and clinical challenges. Ageing Res Rev. 2024;98:102344. doi:10.1016/j.arr.2024.102344.
19. Ekundayo OJ, Allman RM, Sanders PW, et al. Isolated systolic hypertension and incident heart failure in older adults: a propensity-matched study. Hypertension. 2009;53(3):458-65. doi:10.1161/HYPERTENSIONAHA.108.119792.
20. Li Y, Wei FF, Thijs L, et al.; International Database on Ambulatory blood pressure in relation to Cardiovascular Outcomes (IDACO) Investigators. Ambulatory hypertension subtypes and 24-hour systolic and diastolic blood pressure as distinct outcome predictors in 8341 untreated people recruited from 12 populations. Circulation. 2014;130(6):46674. doi:10.1161/CIRCULATIONAHA.113.004876.
21. Liu J, Bu X, Wei L, et al. Global burden of cardiovascular diseases attributable to hypertension in young adults from 1990 to 2019. J Hypertens. 2021;39(12):2488-96. doi:10.1097/HJH.0000000000002958.
22. McEniery CM, Franklin SS, Cockcroft JR, Wilkinson IB. Isolated Systolic Hypertension in Young People Is Not Spurious and Should Be Treated: Pro Side of the Argument. Hypertension. 2016;68(2):269-75. doi:10.1161/HYPERTENSIONAHA.116.06547.
23. Mancia G, Giannattasio C. Diagnostic and therapeutic problems of isolated systolic hypertension. J Hypertens. 2015;33:33-43. doi:10.1097/HJH.0000000000000424.
24. Yano Y, Reis JP, Colangelo LA, et al. Association of blood pressure classification in young adults using the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline with cardiovascular events later in life. JAMA. 2018;320:1774-82. doi:10.1001/jama.2018.13551.
25. Lee H, Yano Y, Cho SMJ, et al. Cardiovascular risk of isolated systolic or diastolic hypertension in young adults. Circulation. 2020;141:1778-86. doi:10.1161/CIRCULATIONAHA.119.044838
26. Yano Y, Reis JP, Lewis CE, et al. Association of blood pressure patterns in young adulthood with cardiovascular disease and mortality in middle age. JAMA Cardiol. 2020;5:382-9. doi:10.1001/jamacardio.2019.5682.
27. Nwabuo CC, Appiah D, Moreira HT, et al. Long-term cumulative blood pressure in young adults and incident heart failure, coronary heart disease, stroke, and cardiovascular disease: the CARDIA study. Eur J Prev Cardiol. 2021;28(13):1445-51. doi:10.1177/2047487320915342.
28. Julius S, Kjeldsen SE, Weber M, et al.; VALUE trial group. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004;363(9426):2022-31. doi:10.1016/S01406736(04)16451-9.
29. Jamerson K, Weber MA, Bakris GL, et al.; ACCOMPLISH Trial Investigators. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359(23):2417-28. doi:10.1056/NEJMoa0806182.
30. Lu F, Zhao Y, Liu Z, et al. A 48-week study of amlodipine plus amiloride / hydrochlorothiazide vs. amlodipine plus telmisartan in the treatment of hypertension. Int J Clin Pract. 2012;66(8):792-9. doi:10.1111/j.1742-1241.2012.02943.x.
31. Matsuzaki M, Ogihara T, Umemoto S, et al.; Combination Therapy of Hypertension to Prevent Cardiovascular Events Trial Group. Prevention of cardiovascular events with calcium channel blocker-based combination therapies in patients with hypertension: a randomized controlled trial. J Hypertens. 2011;29(8):1649-59. doi:10.1097/HJH.0b013e328348345d.
32. Ojji DB, Mayosi B, Francis V, et al.; CREOLE Study Investigators. Comparison of Dual Therapies for Lowering Blood Pressure in Black Africans. N Engl J Med. 2019;380(25):2429-39. doi:10.1056/NEJMoa1901113.
33. Beckett NS, Peters R, Fletcher AE, et al.; HYVET Study Group. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358(18):1887-98. doi:10.1056/NEJMoa0801369.
34. PATS Collaborating Group. Post-stroke antihypertensive treatment study. A preliminary result. Chin Med J (Engl). 1995;108(9):710-7.
35. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressurelowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358(9287):1033-41. doi:10.1016/S0140-6736(01)06178-5.
36. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and LipidLowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288(23):2981-97. doi:10.1001/jama.288.23.2981.
37. Dahlöf B, Sever PS, Poulter NR, et al.; ASCOT Investigators. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet. 2005;366(9489):895-906. doi:10.1016/S0140-6736(05)67185-1.
38. Nissen SE, Tuzcu EM, Libby P, et al.; CAMELOT Investigators. 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):2217-25. doi:10.1001/jama.292.18.2217.
39. Pitt B, Byington RP, Furberg CD, et al. Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. PREVENT Investigators. Circulation. 2000;102(13):1503-10. doi:10.1161/01.cir.102.13.1503.
40. Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet. 1997;350(9080):757-64. doi:10.1016/s0140-6736(97)05381-6.
41. Hansson L, Lindholm LH, Ekbom T, et al. Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study. Lancet. 1999;354(9192):1751-6. doi:10.1016/s0140-6736(99)10327-1.
42. Liu L, Wang JG, Gong L, et al. Comparison of active treatment and placebo in older Chinese patients with isolated systolic hypertension. Systolic Hypertension in China (SystChina) Collaborative Group. J Hypertens. 1998;16(12 Pt 1):1823-9. doi:10.1097/00004872199816120-00016.
43. Turnbull F, Neal B, Ninomiya T, et al. Effects of different regimens to lower blood pressure on major cardiovascular events in older and younger adults: meta-analysis of randomised trials. BMJ. 2008;336(7653):1121-3. doi:10.1136/bmj.39548.738368.BE.
44. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338: b1665. doi:10.1136/bmj.b1665.
45. Akram J, Sheikh UE, Mahmood M, Donnelly R. Antihypertensive efficacy of indapamide SR in hypertensive patients uncontrolled with a background therapy: the NATIVE study. Curr Med Res Opin. 2007;23(12):2929-36. doi:10.1185/030079907X242674.
46. Jadhav U, Hiremath J, Namjoshi DJ, et al. Blood pressure control with a single-pill combination of indapamide sustained-release and amlodipine in patients with hypertension: the EFFICIENT study. PLoS One. 2014;9(4):e92955. doi:10.1371/journal.pone.0092955.
47. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991;265(24):3255-64.
48. Emeriau JP, Knauf H, Pujadas JO, et al.; European Study Investigators. A comparison of indapamide SR 1.5 mg with both amlodipine 5 mg and hydrochlorothiazide 25 mg in elderly hypertensive patients: a randomized double-blind controlled study. J Hypertens. 2001;19(2):343-50. doi:10.1097/00004872-200102000-00023.
49. Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party. BMJ. 1992;304(6824):405-12. doi:10.1136/bmj.304.6824.405.
50. Lurbe E, Redon J. Isolated Systolic Hypertension in Young People Is Not Spurious and Should Be Treated: Con Side of the Argument. Hypertension. 2016;68(2):276-80. doi:10.1161/HYPERTENSIONAHA.116.06548.
51. Kiru G, Roy A, Kondal D, et al.; TOPSPIN Investigators. Treatment optimisation for blood pressure with single-pill combinations in India (TOPSPIN) — Protocol design and baseline characteristics. Int J Cardiol Cardiovasc Risk Prev. 2024;23:200346. doi:10.1016/j.ijcrp.2024.200346.
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Kobalava Zh.D., Troitskaya E.A. Fixed-dose combination of indapamide and amlodipine in the treatment of isolated systolic hypertension: analysis of the ARBALET study. Russian Journal of Cardiology. 2025;30(8):6486. (In Russ.) https://doi.org/10.15829/1560-4071-2025-6486. EDN: CNUCOE
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