Fixed combination of amlodipine/indapamide-retard in the treatment of uncontrolled hypertension in subjects over 55 years old

Objective. To evaluate the antihypertensive efficacy and safety of a fixed combination of amlodipine/indapamideretard in patients with uncomplicated uncontrolled arterial hypertension (HTN) in the older age group. Design and methods. We included 40 patients (average age — 62 years, men — 20 %, mean HTN duration — 9 years) with uncomplicated uncontrolled HTN in an open, single-center study. Fixed-combination therapy with amlodipine/indapamide-retard (5/1,5 mg) once a day for 4 weeks were prescribed. After 4 weeks, in patients who did not reach the target blood pressure (BP), the dose increased from 5/1,5 to 10/1,5 mg. The follow-up period was 12 weeks. Results. The initial systolic BP (SBP) was 165 [148; 171] mm Hg, diastolic BP (DBP) — 96 [80; 102] mm Hg. After a 12-week therapy with a fixed combination of amlodipine/indapamide-retard, SBP decreased by 31 mm Hg, DBP — by 17 mm Hg. Target clinical BP (< 140/90 mm Hg in patients without diabetes mellitus (DM), < 140/85 mm Hg in patients with diabetes mellitus) was achieved in 93 % patients. Central SBP measured by applanation tonometry decreased by 16 mm Hg, DBP — 10 mmHg, pulse pressure — 6 mmHg. Prior to treatment, the median of carotid-femoral pulse wave velocity (cfPWV) was 11,1 [7,8; 14,5] m/sec. After 12 weeks there was a decrease in cfPWV to 8,9 [6,7; 12,6] m/sec (p < 0,05 in comparison with the baseline). Conclusions. Fixed combination of amlodipine/thiazide-like diuretic in patients with uncomplicated uncontrolled 1–2 degree HTN has a high antihypertensive efficacy, allowing achievement of target BP in 93 % patients after 12-week therapy, with a satisfactory safety profile and metabolic neutrality. We showed the ability of a combination of amlodipine/indapamide-retard to reduce central SBP, pulse pressure in the aorta, and cfPWV.

amlodipine, indapamide-retard, antihypertensive efficacy, safety

1. Шальнова С. А., Деев А. Д., Оганов Р. Г., Шестов Д. Б. Роль систолического и диастолического артериального давления для прогноза смертности от сердечно-сосудистых заболеваний. Кардиоваскулярная терапия и профилактика. 2002;1:10–15. [Shalnova SA, Deev AD, Oganov RG, Shestov DB. The prognostic role of systolic and diastolic blood pressure for cardiovascular morbidity. Kardiovaskulyarnaya Terapiya i Profilaktika = Cardiovascular Therapy and Prevention. 2002;1:10–15 In Russian].

2. Моисеев В. С., Кобалава Ж. Д. АРГУС: артериальная гипертония у лиц старших возрастных групп. М.: МИА, 2002. 448 с. [Moiseev VS, Kobalava ZhD. ARGUS: hypertension in elderly patients. M.: MIA, 2002. 448 p. In Russian].

3. Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhäger WH 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):757–764.

4. 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). SHEP Cooperative Research Group. J Am Med Assoc. 1991;265 (24):3255–3264.

5. Lindholm LH, Hansson L, Dahlöf B, Ekbom T, Hedner T, De Faire U et al. The Swedish Trial in old patients with hypertension-2 (STOP-hypertension-2): a progress report. Blood Press. 1996;5 (5):300–304.

6. Agnoletti D, Zhang Yi, Borghi C, Blacher J, Safar ME. Effects of antihypertensive drugs on central blood pressure in humans: a preliminary observation. Am J Hypertens. 2013;26 (8):1045–1052.

7. Rimoldi SF, Messerli FH, Chavez P, Stefanini GG, Scherrer U et al. Efficacy and safety of calcium channel blocker/diuretics combination therapy in hypertensive patients: a meta-analysis. J Clin Hypertens. 2015;17(3):193–199.

8. Aronow WS, Fleg JL, Pepine CJ, Artinian NT, Bakris G, Brown AS et al. ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation. 2011;123(21):2434–2506.

9. 2018 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension and the European Society of Cardiology: ESH/ESC Task Force for the management of arterial hypertenion. J Hypertens. 2018;36 (12):2284–2309. doi:10.1097/HJH.0000000000001961

10. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in highrisk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288(23):2981–2997.

11. Liu L, Wang JG, Gong L, Liu G, Staessen JA. Comparison of active treatment and placebo in older Chinese patients with isolated systolic hypertension. Systolic Hypertension in China (Syst-China) Collaborative Group. J Hypertens. 1998;16(12 Pt 1): 1823.

12. Jamerson K, Weber MA, Bakris GL, Dahlöf B, Pitt B, Shi V et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359(23): 2417–2428.

13. Baguet JP, Legallicier B, Auquier P, Robitail S. Updated meta-analytical approach to efficacy of antihypertensive drugs in reducing blood pressure. Clinical Drug Invest. 2007;27(11):735– 753.

14. Кобалава Ж. Д., Шаварова Е. К. Клинические особенности артериальной гипертонии в пожилом и старческом возрасте и обоснование применения комбинации амлодипин/индапамид ретард. Кардиология. 2017;57(8):60–70. [Kobalava ZhD, Shavarova EK. Clinical features of arterial hypertension in the elderly and senile age and the rationale for using the combination of amlodipine/indapamide-retard. Kardiologiia. 2017;57(8):60–70. In Russian].

15. Alderman MH, Cohen HW, Sealey JE, Laragh JH. Pressor responses to antihypertensive drug types. Am J Hypertens. 2010;23 (9):1033–1037.

16. Furberg CD. Renin-guided treatment of hypertension: time for action. Am J Hypertens. 2010;23(9):929–930.

17. Brown MJ. Heterogeneity of blood pressure response to therapy. Am J Hypertens. 2010;23(9):926–928.

18. Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A, Collier D et al. on behalf the CAFÉ Investigators. Differential impact of blood pressure — lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation. 2006;113(9):1213–1225.

19. Cecelja M, Chowienczyk P. Dissociation of aortic pulse wave velocity with risk factors for cardiovascular disease other than hypertension: a systematic review. Hypertension. 2009;54(6): 1328–1336.

20. Burke GL, Bertoni AG, Shea S, Tracy R, Watson KE, Blumenthal RS, et al. The impact of obesity on cardiovascular disease risk factors and subclinical vascular disease: the MultiEthnic Study of Atherosclerosis. Arch Intern Med. 2008;168 (9):928–935.

21. Mitchell GF, Hwang S-J, Vasan RS, Larson MG, Pencina MJ, Hamburg NM et al. Arterial stiffness and cardiovascular events: the Framingham Heart Study. Circulation. 2010;121(4):505–511.