Implementation of the organoprotective properties of fixed combinations of valsartan, amlodipine and hydrochlorothiazide (Vamloset® and Co-Vamloset) in patients with grade 2 and 3 hypertension in the Russian clinical study VICTORY II

Abstract

Aim.Assessment of Vamloset and Co-Vamloset effects on blood pressure target levels and indicators associated with organ protection: albuminuria; elasticity of arteries and central aortic pressure (CAP); endothelial function; tumor necrosis factor-a, interleukin (IL) IL-6 and IL-10, vascular cell adhesion molecule 1 and vascular endothelial growth factor (VEGF-A).
 Materials and methods.The Russian multicenter open-label prospective clinical study VICTORY II which was conducted in 8 clinical centers included 103 patients 18 years with grade 23 essential arterial hypertension (AH), who were previously untreated office systolic blood pressure (SBP) 160mmHg and/or office diastolic blood pressure (DBP) 100 mm Hg or have not reached the target office blood pressure with mono- or dual therapy. The active phase of the study included 100 patients; the per-protocol (PP) population 80 patients completing the study without major protocol deviations. Patients were not randomized. The target office BP for patients without diabetes were: SBP139 mm Hg, DBP89 mm Hg; for patients with diabetes: SBP139 mm Hg, DBP84 mm Hg. All patients with grade 2 hypertension (group 1) were administrated Vamloset (amlodipine/valsartan, 5/80mg), with grade 3 hypertension Vamloset (amlodipin/valsartan, 5/160 mg). Up-titration of the dose of amlodipine/valsartan to 5/160 mg and 10/160 mg, the administration of Co-Vamloset (amlodipine/valsartan/hydrochlorothiazide) in doses of 10/160/12.5 mg, 10/160/25 mg (LLC KRKA-RUS) was carried out every 4 weeks according to the prescribed schemes. In the total group, the effect of studied therapy on the level of albumin in the urine was assessed. Before starting treatment and after 16 weeks of treatment, 40 patients in the subgroup with additional examinations underwent daily monitoring of blood pressure, assessment of pulse wave velocity and augmentation index; CAP; levels of tumor necrosis factor-, IL-6 and IL-10, vascular cell adhesion molecule 1and VEGF-A.
 Results.The active phase of the study included 100 patients aged 59.510.9 years (59% of women) with a duration of AH 83.48.4 months. 83% of patients received prior antihypertensive therapy by the time of enrollment in the study. The treatment duration for all patients was 15.9 weeks. After 16 weeks, therapy with Vamloset and Co-Vamloset provided an optimal decrease in BP: 90% of patients with grade 23 AH in the PP population reached the target level of office BP, the mean change in SBP / DBP was -32.2/-16.0 mm Hg. According to the data of daily monitoring of BP in the subgroup with additional examinations, the target levels of average daily SBP/DBP were reached in 52.9/67.6% of patients, respectively. Along with reliable control of blood pressure, additional organ protection with studied antihypertensive drugs after 16 weeks of therapy was shown by assessment data: albuminuria in 58.8% of patients with an initially elevated level of albuminuria (n=17), a positive effect of the studied therapy on the level of albumin in the urine was determined, augmentation index improvement in 57.1% of patients in the study group, CAP improvement in 73% of patients in the study group; positive dynamics of endothelial damage markers (IL-6, IL-10, VEGF-A) was achieved. The data on the good tolerability of AHT corresponded to the previously established safety profile of these drugs.
 Conclusion.In the VICTORY II clinical study in patients with grade 23 hypertension, along with high antihypertensive efficacy, a spectrum of organoprotective effects of Vamloset and Co-Vamloset on aortic stiffness with improved augmentation index and CAP, markers of endothelial damage (IL-6, IL-10, VEGF-A), the severity of albuminuria was shown.