The influence of antyhypertensive therapy of valsartan and fixed combination with hydrochlorothiazide use on pulse-wave velocity and central arterial pressure in patients with arterial hypertension of 1-2 grades in international VICTORY clinical trial

Objective - to explore influence of valsartan monotherapy use and its use in combination with hydrochlorothiazide (HCTZ) on pulse-wave velocity (PWV) and central arterial pressure (CAP) in patients with arterial hypertension (AH) of 1-2 grades in international VICTORY clinical trial. Materials and methods. The international multicenter prospective randomized clinical study VICTORY that lasted for 16 weeks included patients with 1-2 grades AH. In patients who previously received antihypertensive therapy a 7 days washout period was carried out. All patients started their therapy with 80 mg valsartan (Valsacor®, KRKA, Slovenia); in Russia the starter dose of Valsacor®, KRKA was 160 mg in previously treated patients that did not influence the study results. If after 4 weeks of treatment BP was more than 140/90 mm hg (more than 130/80 mm hg in high risk patients or in diabetes mellitus patients) the dose of valsartan was increased to 160 mg (320 mg in Russia) or diuretic in fixed combination with valsartan was added (160 mg valsartan/12.5 mg HCTZ): Valsacor® H 160 (KRKA, Slovenia). If target BP after 8 weeks of treatment was not reached valsartan dose was increased to 320 mg or fixed combination of valsartan and diuretic (160 mg/12.5 mg) was used. If target BP after 12 weeks of treatment was not reached - valsartan and diuretic 320 mg/12.5 mg were used. PWV and CAP (SphygmoCor®, AtCorMedical) were assessed at baseline and after 16 weeks of treatment. The primary endpoints were assessment of the impact of studied medications on aortic stiffness, aortic augmentation index and comparison of absolute medians of reached central and peripheral BP reduction with baseline value. Results. Of 365 patients included in the study 74 were included in PWV and CAP study subgroup. Valsartan and its combination with HCTZ were effective in CBP reduction. The mean absolute reduction of central systolic and diastolic BP after 16 weeks of treatment was 19.7±12.9 mm hg and 13.9±8.5 mm hg, respectively (р<0.0001). PWV at 16 weeks was statistically significant (p<0.0001). The mean aortic augmentation index value did not change significantly (p=0.855). Conclusions. In VICTORY study valsartan use for 16 weeks as monotherapy (Valsacor®) and in combination with HCTZ (Valsacor®H) resulted in aortic stiffness reduction in patients with 1-2 grades AH, that may lead to patients' prognosis improvement and risk of cardiovascular events reduction.

валсартан, гидрохлоротиазид, артериальная гипертония, скорость пульсовой волны, центральное артериальное давление, клиническое исследование VICTORY

1. Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2013; 31 (7): 1281-357.

2. Чазова И.Е., Ощепкова Е.В., Жернакова Ю.В. Клинические рекомендации диагностика и лечение артериальной гипертонии. Кардиологический вестн. 2015; 1: 3-30

3. The Task Force for the management of arterial hypertension of the European Society of Hypertension and of the European Society of Cardiology. 2007 Guidelines for the management of arterial hypertension. J Hypertens 2007; 25: 1105-87.

4. Weber M.A, Julius S, Kjeldsen S.E et al. Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial. Lancet 2004; 363: 2049-51.

5. Parati G, Asmar R, Bilo G et al. Effectiveness and safety of high-dose valsartan monotherapy in hypertension treatment: the ValTop study. Hypertens Res 2010; 33 (10): 986-94.

6. Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol 2010; 55 (13): 1318-27.

7. Недогода С.В. Скорость распространения пульсовой волны как фактор риска развития сердечно-сосудистых осложнений и мишень для фармакотерапии. Фарматека 2010; 8 (202): 18-26

8. Roman M.J, Devereux R.B, Kizer J.R et al. Central pressure more strongly relates to vascular disease and outcome than does brachial pressure: the Strong Heart Study. Hypertension 2007; 50: 197-203.

9. Чазова И.Е., Мартынюк Т.В. от имени группы российских исследователей. Первые результаты международного клинического исследования VICTORY: эффективность и безопасность антигипертензивной монотерапии валсартаном и его фиксированной комбинации с гидрохлоротиазидом в разных дозовых режимах у пациентов с артериальной гипертонией 1-2-й степени. Системные гипертензии. 2015; 12 (2): 71-82

10. Чазова И.Е., Мартынюк Т.В. Диуретики в составе комбинированной антигипертензивной терапии: фокус на прогноз. Системные гипертензии. 2016; 13 (2): 6-10.

11. Laurent S, Boutouyrie P, Asmar R et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001; 37: 1236-41.

12. Asmar R.G, London G.M, O’Rourke M.E. REASON Project Coordinators and Investigators: Improvement in blood pressure, aortic stiffness and wave reflections with a very-low-dose perindopril/indapamide combination in hypertensive patient: a comparison with atenolol. Hypertension 2001; 38: 922-6.

13. Accetto R, Chazova I, Sirenko Y et al. The efficacy and safety of valsartan and combination of valsartan and hydrochlorothiazide in the treatment of patients with mild to moderate arterial hypertension - the VICTORY trial. Kardiol Pol 2018; 76 (2): 328-37.

14. Boutouyrie P, Tropeano A.I, Asmar R et al. Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: a longitudinal study. Hypertension 2002; 39: 10-5.

15. Nakamura T, Fujii S, Hoshino J et al. Selective angiotensin receptor antagonism with valsartan decreases aortic stiffness independently of blood pressure lowering in hypertensive patients. Hypertens Res 2005; 28 (12): 937-43.

16. Karalliedde J, Smith A, DeAngelis L et al. Valsartan improves aortic stiffness in type 2 diabetes independently of blood pressure lowering. Hypertension 2008; 51 (6): 1617-23.

17. Periard D, Rey M.A, Casagrande D et al. The effect of valsartan versus non-RAAS treatment on autoregulation of cerebral blood flow. Cerebrovasc Dis 2012; 34 (1): 78-85.

18. Black H.R, Bailey J, Zappe D et al. Valsartan: more than a decade of experience. Drugs 2009; 69 (17): 2393-414.

19. Accetto R, Widimsky J, Vincelj J, et al. The efficacy and safety of valsartan and a combination of valsartan and hydrochlorothiazide in the treatment of patients with mild to moderate arterial hypertension: a subgroup analysis of the effect of valsartan and its combination with hydrochlorothiazide on pulse wave velocity and central blood pressure. Kardiologia Polska 2018; 76, 2: 328-337; DOI: 10.5603/KP.a2017.0240.

20. Stewart A.D, Jiang B, Millasseau S.C et al. Acute reduction of blood pressure by nitroglycerin does not normalize large artery stiffness in essential hypertension. Hypertension 2006; 48: 404-10.