Dose Of Valsartan Research Articles

The results of the international clinical study VICTORY: efficacy and safety of antihypertensive monotherapy with valsartan (Valsacor®) and its fixed combination with hydrochlorothiazide (Valsacor® H) in routine clinical practice in patients with grade 1 and grade 2 hypertension

Objective. The VICTORY study aimed to evaluate effectiveness and safety of monotherapy with valsartan (Valsacor®) and its fixed combination with hydrochlorothiazide (Valsacor® H) in clinical practice in patients with stage 1 and stage 2 hypertension. Materials and methods. In the prospective, randomized, open-label, international multicentre study involved 356 patients with grade 1 and grade 2 hypertension from 5 countries, including 130 patients from Russia. In Russia the study was conducted in 7 cities, in 8 clinical centers. The patients, who were receiving antihypertensive therapy at the moment of screening, underwent a 7 days wash-out period. The starter dose of valsartan (Valsacor®, KRKA, Slovenia) was 80 mg (except for Russia where 160 mg of Valsacor® were given at the first visit, what did not influence the study results). After 4 weeks of treatment in case of blood pressure (BP) >140/90 or 130/80 mm Hg the dose was increased to 160 mg (in Russia - to 320 mg) or combined therapy with Valsacor® H (KRKA, Slovenia) was prescribed. In 4 weeks the dose of valsartan was increased to 320 or 160/12.5 mg in case of previous dose insufficiency. If target BP levels were not reached in the next 4 weeks, the dose was increased to 320/12.5 mg. The primary endpoints included evaluation of antihypertensive effect of valsartan and its fixed combination with hydrochlorothiazide on BP levels; evaluation of the drugs’ influence on aortal stiffness; comparison of absolute average means of achieved decrease in central and peripheral BP compared with baseline; evaluation of the impact on aortic augmentation index. The secondary endpoints included comparison of primary endpoints when using mono and combined therapy; evaluation and comparison of the effect on erectile function in men by questionnaires at baseline and after 16 weeks of treatment; evaluation of adverse events frequency. Results. Data on 365 patients - 196 (54.0%) female and 169 (46.0%) male aged 54.6±12.0 years were analyzed. Mean initial value of systolic (SBP) and diastolic BP (DBP) were 156.6±8.9 and 95.6±6.0 mm Hg, respectively and 130.1±8.2 and 80.9±5.8 mm Hg, respectively after 16 weeks of treatment. The mean absolute decrease of SBP and DBP was 26.6±10.4 and 14.8±7.6 mm Hg. The decrease of SBP and DBP was statistically significant in all treatment periods (p

Итоги международного клинического исследования VICTORY: эффективность и безопасность антигипертензивной монотерапии валсартаном (Вальсакор®) и его фиксированной комбинации с гидрохлоротиазидом (Вальсакор® Н) у пациентов с артериальной гипертонией 1–2-й степени в рутинной клинической практике

Objective. The VICTORY study aimed to evaluate effectiveness and safety of monotherapy with valsartan (Valsacor®) and its fixed combination with hydrochlorothiazide (Valsacor® H) in clinical practice in patients with stage 1 and stage 2 hypertension. Materials and methods. In the prospective, randomized, open-label, international multicentre study involved 356 patients with grade 1 and grade 2 hypertension from 5 countries, including 130 patients from Russia. In Russia the study was conducted in 7 cities, in 8 clinical centers. The patients, who were receiving antihypertensive therapy at the moment of screening, underwent a 7 days wash-out period. The starter dose of valsartan (Valsacor®, KRKA, Slovenia) was 80 mg (except for Russia where 160 mg of Valsacor® were given at the first visit, what did not influence the study results). After 4 weeks of treatment in case of blood pressure (BP) >140/90 or 130/80 mm Hg the dose was increased to 160 mg (in Russia - to 320 mg) or combined therapy with Valsacor® H (KRKA, Slovenia) was prescribed. In 4 weeks the dose of valsartan was increased to 320 or 160/12.5 mg in case of previous dose insufficiency. If target BP levels were not reached in the next 4 weeks, the dose was increased to 320/12.5 mg. The primary endpoints included evaluation of antihypertensive effect of valsartan and its fixed combination with hydrochlorothiazide on BP levels; evaluation of the drugs’ influence on aortal stiffness; comparison of absolute average means of achieved decrease in central and peripheral BP compared with baseline; evaluation of the impact on aortic augmentation index. The secondary endpoints included comparison of primary endpoints when using mono and combined therapy; evaluation and comparison of the effect on erectile function in men by questionnaires at baseline and after 16 weeks of treatment; evaluation of adverse events frequency. Results. Data on 365 patients - 196 (54.0%) female and 169 (46.0%) male aged 54.6±12.0 years were analyzed. Mean initial value of systolic (SBP) and diastolic BP (DBP) were 156.6±8.9 and 95.6±6.0 mm Hg, respectively and 130.1±8.2 and 80.9±5.8 mm Hg, respectively after 16 weeks of treatment. The mean absolute decrease of SBP and DBP was 26.6±10.4 and 14.8±7.6 mm Hg. The decrease of SBP and DBP was statistically significant in all treatment periods (p<0,0001). The mean absolute decrease of central SBP and DBP at the 5th visit was 19.7±12.9 and 13.9±8.5 mm Hg, respectively (p<0.0001). When compared, the mean values of SBP and DBP between groups of mono and combined therapy were statistically significant (p<0.0001). 90,6% of patients reached the target BP levels: 98% in those who received monotherapy with valsartan and 84% in those who received combination of valsartan and hydrochlorothiazide. The mean absolute increase of erectile function score was 0.84±2.45 (p<0.0001). There were no differences in erectile function score dynamics in the two groups of patients. 92.8% of patients did not experience adverse effects and adverse events associated with the medication. There were no cases of severe adverse events in the study. The most frequent adverse effects were headache (1.9%), dizziness (1.6%), and weakness (1.6%). Conclusion. The study demonstrated high effectiveness and good tolerability of valsartan and its fixed combination with hydrochlorothiazide (Valsacor®, Valsacor® H) in patients with stage 1 and stage 2 hypertension. 1. Valsartan in monotherapy (Valsacor®) and in combination with hydrochlorothiazide (Valsacor® H) lowers the SBP and DBP levels to reference levels. 2. At the 16th week of treatment 90.6% reached target BP levels: 98% in the valsartan monotherapy group and 84% in the combination therapy with valsartan and hydrochlorothiazide group. 3. The medications Valsacor® and Valsacor® H have good tolerability: 92.8% of the patients did not experience any adverse effects. 7.1% of patients had at least 1 adverse effect but none of them experienced any severe adverse events. 4. The therapeutic effect was estimated as good and very good in 96.9% of patients. 5. The overall clinical effectiveness was estimated as excellent, very good and good in 95.3% of patients. 6. Most of the patients receiving Valsacor® and Valsacor® H noted an increase in life quality. 7. Treatment with Valsacor® and Valsacor® H resulted in increase of erectile function in male patients with stage 1 and stage 2 hypertension.

PP.26.07] IMPACT OF VALSARTAN AND COMBINATION OF VALSARTAN AND HYDROCHLOROTHIAZIDE ON ERECTILE DYSFUNCTION IN PATIENTS WITH MILD TO MODERATE HYPERTENSION

Objective: Erectile dysfunction is recognised quality of life disorder frequently occurring in hypertensive patients. It can be caused by high blood pressure per se or due to antihypertensive treatment. Diuretics and -blockers (except nebivolol) are the drugs most commonly linked to erectile dysfunction. ACE inhibitors and calcium antagonists seem to exert neutral effects, while ARBs seem to be associated with beneficial effects on erectile function. The aim of our study was to assess the effect of treatment with valsartan and valsartan-HCTZ on erectile function. Design and method: We assessed erectile dysfunction in 98 patients, aged 40 – 79 years, with mild to moderate hypertension, participating in international, multicentre, open labelled trial – VICTORY (sponsored by KRKA, d.d.) using the questionnaire IIEF-5, before and after 16 week of treatment with valsartan or valsartan-HCTZ. The treatment was initiated with 80 mg of valsartan daily. After four weeks of treatment the dose was increased to 160 mg valsartan daily in patients who did not achieve goal blood pressure. If target blood pressure was not achieved after consequent 4 weeks the dose of valsartan was further increased to 320 mg daily or fixed combination of valsartan-HCTZ 160/12.5 mg daily was implemented. At next visit, after additional 4 weeks, in patients who did not achieve goal blood pressure, the dose of fixed combination was increased to 320/12.5 mg of valsartan-HCTZ daily. Results: At the end of the trial, in 90.6% of patients, the goal blood pressure, according to 2013 ESH/ESC Guidelines for the management of arterial hypertension, was achieved. The slight statistically significant increase in mean IIEF-5 score after 16 weeks of treatment was observed in patients on monotherapy with valsartan and in patients on combination therapy with valsartan-HCTZ which was introduced on visit 3 or visit 4 (from 23.5 7.7 to 24.1 8.1, and from 23.8 5.0 to 24.2 6.7, respectively). Conclusions: Goal blood pressure was achieved in 90.6% of patients. Treatment with valsartan as well as adding low dose of HCTZ to valsartan did not lead to deterioration of erectile function in patients with mild to moderate hypertension.

Safety of the Up-titration of Nifedipine GITS and Valsartan or Low-dose Combination in Uncontrolled Hypertension: the FOCUS Study

PurposeDoubling the dose of antihypertensive drugs is necessary to manage hypertension in patients whose disease is uncontrolled. However, this strategy can result in safety issues. This study compared the safety and efficacy of up-titration of the nifedipine gastrointestinal therapeutic system (GITS) with up-titration of valsartan monotherapy; these were also compared with low-dose combinations of the two therapies. MethodsThis prospective, open-label, randomized, active-controlled, multicenter study lasted 8 weeks. If patients did not meet the target blood pressure (BP) after 4 weeks of treatment with low-dose monotherapy, they were randomized to up-titration of the nifedipine GITS dose from 30 mg (N30) to 60 mg or valsartan from 80 mg to 160 mg or they were randomized to receive a low-dose combination of N30 and valsartan 80 mg for another 4 weeks. BP variability was assessed by using the SD or the %CV of the short-term BP measured at clinic. FindingsOf the 391 patients (20~70 years with stage II or higher hypertension) screened for study inclusion, 362 patients who had 3 BP measurements were enrolled. The reduction in the mean systolic/diastolic BP from baseline to week 4 was similar in both low-dose monotherapy groups with either N30 or valsartan 80 mg. BP variability (SD) was unchanged with either therapy, but the %CV was slightly increased in the N30 group. There was no significant difference in BP variability either in SD or %CV between responders and nonresponders to each monotherapy despite the significant difference in the mean BP changes. The up-titration effect of nifedipine GTS from 30 to 60 mg exhibited an additional BP reduction, but this effect was not shown in the up-titration of valsartan from 80 to 160 mg. Although the difference in BP was obvious between high-dose nifedipine GTS and valsartan, the BP variability was unchanged between the 2 drugs and was similar to the low-dose combinations. There was a low rate of adverse events in all treatment groups. In addition, escalating the dose of either nifedipine GITS or valsartan revealed a similar occurrence of adverse effects with low-dose monotherapy or the low-dose combination. ImplicationsCompared with up-titration of the angiotensin receptor blocker valsartan, up-titration of the calcium channel blocker nifedipine GITS provided no additional increased safety concerns and revealed better mean reductions in BP without affecting short-term BP variability. ClinicalTrials.gov identifier: NCT01071122.

Efficacy and safety of supramaximal titrated inhibition of renin-angiotensin-aldosterone system in idiopathic dilated cardiomyopathy.

AimsThe optimal dosing strategies for blocking the renin‐angiotensin‐aldosterone system in idiopathic dilated cardiomyopathy (IDCM) are poorly known. We sought to determine the long‐term efficacy and safety of supramaximal titration of benazepril and valsartan in patients with IDCM.Methods and results480 patients with IDCM in New York Heart Association functional class II–IV and with left ventricular ejection fraction ≤35% were randomly assigned to extended‐release metoprolol (mean 152 mg/day, range 23.75–190), low‐dose benazepril (20 mg/day), low‐dose valsartan (160 mg/day), high‐dose benazepril (mean 69 mg/day, range 40–80), and high‐dose valsartan (mean 526 mg/day, range 320–640). After a median follow‐up of 4.2 years, high‐dose benazepril and valsartan, compared with their respective low dosages, resulted in 41% and 52% risk reduction in the primary endpoint of all‐cause death or admission for heart failure (P = 0.042 and 0.002), promoted functional improvement, and reversed remodelling as assessed by New York Heart Association classes, quality‐of‐life scores, and echocardiographic recording of left ventricular ejection fraction, left ventricular end‐diastolic volume, mitral regurgitation, and wall motion score index. Compared with metoprolol, high‐dose valsartan reduced risk for the primary endpoint by 46% (P = 0.006), whereas high‐dose benazepril and both low‐dose groups showed no significant difference. Major adverse events involved hypotension and renal impairment but were largely tolerated.ConclusionsSupramaximal doses of benazepril and valsartan were well tolerated and produced extra benefit than their low dosages in clinical outcome and cardiac reverse remodelling in patients with IDCM and modest‐severe heart failure. ClinicalTrials.gov identifier: NCT01917149.

The first results of an international clinical trial VICTORY:the efficacy and safety of antihypertensive valsartan monotherapy and the fixed combination of valsartan and hydrochlorothiazide usingdifferent dosage regimens in patients with 1-2 degree arterial hypertension

On behalf of the group of russian researchers. The aim of the VICTORY study was to estimate the efficacy and safety of valsartan monotherapy using different dose regimes (Valsacor® 80, 160, 320 mg) and its fixed combination with hydrochlorothiazide (HCTZ) using different dosage regimens [Valsacor® H160 (valsartan 160 mg + HCTZ12.5 mg), Valsacor® H320 (valsartan 320 mg + HCTZ 12.5 mg) Valsacor® HD320 (valsartan 320 mg + HCTZ 25 mg)] in reaching the target level of blood pressure (BP) in patients with 1-2 degree arterial hypertension (AH).Materials and methods. There are 130 patients with 1-2 degree AH were enrolled in the open international multicenter prospective randomized study from 7 cities in 8 Russian Clinical Centers in Russia. The starting dose of valsartan depended upon the previous antihypertensive treatment: for previously untreated patients - 80 mg (Valsacor® 80 mg, KRKA, Slovenia) with randomization into 4 parallel groups (n=108) for the patients receiving antihypertensive therapy during the screening, after washout 7-day period of Valsacor® 160 mg application with randomization into 8 parallel groups (n=22). Besides the dynamics of clinical BP, we evaluated the impact of therapy on pulse ware velocity, erectile function (in men) and the quality of life. Results. The clinical BP in 130 patients with AH with age of 55.6±11.5 years (65% women) at the moment of inclusion into the study was 157.6/95.1 mm Hg. The BP was reduced to 140.9/85.3 mm Hg on the 4-week of valsartan 80 or 160 mg application. Valsartan titration or the combination of valsartan and HCTZ on the 8-week helped to reduce BP to 135.2/83.5 mm Hg. The 16-week treatment showed the BP reduced to 129.2/79.4 mm Hg. ( p

A Combination of Low Doses of Fluvastatin and Valsartan Decreases Arterial Stiffness in Patients After Myocardial Infarction: A Pilot Study

BackgroundDespite optimum treatment, patients who experience myocardial infarction are still at high risk for future events. ObjectiveWe evaluated the effect of 30 days of treatment with combination of low, subtherapeutic doses of fluvastatin and valsartan on arterial stiffness in patients after myocardial infarction, a therapy that has not been used yet. MethodsFourteen male patients with a history of myocardial infarction were enrolled into a pilot double-blind randomized controlled study. They were allocated to receive 10 mg fluvastatin and 20 mg valsartan or placebo for 30 days in addition to their regular pharmacotherapy. Carotid–femoral pulse wave velocity was measured on inclusion, after 30 days, and after 3 months. ResultsMean (SD) carotid–femoral pulse wave velocity decreased significantly in the treatment group after 30 days and persisted at lower values after 3 months (from 8.4 [1.5] m/sec to 7.3 [1.1] m/sec to 7.2 [0.8] m/sec; P < 0.05). The 95% CI for decrease after 30 days in the treatment group was 0.5–1.6. Only nonsignificant changes were observed in the control group. Serum lipid levels and arterial blood pressure did not change significantly in any group. ConclusionsThe treatment resulted in a significant and sustained improvement of arterial stiffness in male patients with a history of myocardial infarction, which highlights the need for further study of this new approach.

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

On behalf of the group of russian researchers. The aim of the VICTORY study was to estimate the efficacy and safety of valsartan monotherapy using different dose regimes (Valsacor® 80, 160, 320 mg) and its fixed combination with hydrochlorothiazide (HCTZ) using different dosage regimens [Valsacor® H160 (valsartan 160 mg + HCTZ12.5 mg), Valsacor® H320 (valsartan 320 mg + HCTZ 12.5 mg) Valsacor® HD320 (valsartan 320 mg + HCTZ 25 mg)] in reaching the target level of blood pressure (BP) in patients with 1-2 degree arterial hypertension (AH).Materials and methods. There are 130 patients with 1-2 degree AH were enrolled in the open international multicenter prospective randomized study from 7 cities in 8 Russian Clinical Centers in Russia. The starting dose of valsartan depended upon the previous antihypertensive treatment: for previously untreated patients - 80 mg (Valsacor® 80 mg, KRKA, Slovenia) with randomization into 4 parallel groups (n=108) for the patients receiving antihypertensive therapy during the screening, after washout 7-day period of Valsacor® 160 mg application with randomization into 8 parallel groups (n=22). Besides the dynamics of clinical BP, we evaluated the impact of therapy on pulse ware velocity, erectile function (in men) and the quality of life. Results. The clinical BP in 130 patients with AH with age of 55.6±11.5 years (65% women) at the moment of inclusion into the study was 157.6/95.1 mm Hg. The BP was reduced to 140.9/85.3 mm Hg on the 4-week of valsartan 80 or 160 mg application. Valsartan titration or the combination of valsartan and HCTZ on the 8-week helped to reduce BP to 135.2/83.5 mm Hg. The 16-week treatment showed the BP reduced to 129.2/79.4 mm Hg. ( p <0.000001). The therapy was statistically significant reducing the level of heart rate and did not affect aortic augmentation index and the condition of erectile function. The percentage of patients who had the departure from normal blood glucose levels, creatinine and potassium, did not increase since the beginning of the study till the 16-week of treatment. Adverse effects were observed in 9.2% of patients, the connection with the drugs was assessed as improbable and in one case as possible, the severity - was moderate or slight.Conclusions:Valsartan monotherapy and the combination of valsartan and HCTZ significantly reduce the systolic BP and diastolic BP to normal levels in patients with 1-2 degree arterial hypertension.As a result of valsartan therapy and the combination with HCTZ the target BP values were achieved at 91% of all patients involved in the study.Valsartan monotherapy and the combination of valsartan and HCTZ led to heart rate reduction and did not affect aortic augmentation index.Therapeutic effect was very good in 89.1% of the patients and good - in 7.0%.The overall clinical efficiency was measured as extremely high in 73.4% of patients, very high - in 15.6% and high - in 6.3%.On assessing the impact of the therapy on the quality of life of patients we noted that 78.7% of patients were in good health, and in 18.1% of cases the treatment did not worsen the general well-being of the patient.

Different chronotherapeutic effects of valsartan and olmesartan in non-dipper hypertensive patients during valsartan treatment at morning

This study was undertaken to evaluate the differences in chronotherapeutic effects of angiotensin-II receptor blockers, valsartan and olmesartan in hypertensive patients with non-dipper blood pressure (BP) pattern during valsartan at morning. Ninety four patients were enrolled, and 40 patients were judged to be non-dippers. In these patients, same dose of valsartan was changed to evening (Val-E, n = 12), or olmesartan (equivalent dose of valsartan) was given at morning (Olm-M, n = 13) or evening (Olm-E, n = 15) for 4 months. BP decreased during sleep and increased during waking hours in Val-E group. In Olm-M and Olm-E groups, BP decreased during sleep and waking hours. Percent reduction in BP at night-time compared to BP at waking hours significantly increased after changing the dose regimen in each group. Serum creatinine decreased and estimated glomerular filtration rate (eGFR) elevated in Olm-M and Olm-E, but not Val-E groups. Positive correlation between systolic BP (SBP) during sleep and serum creatinine, and negative correlation between SBP during sleep and eGFR were detected. These data suggest that dipper BP pattern could be obtained by chronotherapeutic approach using valsartan and olmesartan in non-dipper patients with valsartan at morning. Morning and evening olmesartan, but not evening valsartan improved renal function in these patients.

The effect of angiotensin-2 receptor blocker valsartan on circulating level of endothelial progenitor cells in diabetic patients with asymptomatic coronary artery disease

BackgroundDecreased circulating endothelial progenitor cells (EPCs) are considered as strong and robust biomarkers for the prediction of cardiovascular outcomes in diabetic populations. The perspectives for modulating EPCs levels in T2DM with known coronary artery disease (CAD) with different drugs, affected mechanisms of improving mobilization of EPCs from tissue, are not still understood. AimsTo evaluate an effect of angiotensin-2 receptor blocker valsartan on circulating level of EPCs in diabetic patients with asymptomatic CAD. MethodsThe study population was structured retrospectively after determining the CAD by contrast-enhanced spiral computed tomography angiography in 126 asymptomatic subjects. All subjects were distributed into two cohorts depending on daily doses of valsartan given. Low (80–160mg daily orally) and high doses (240–320mg daily orally) of valsartan were used and they were adjusted depending on achieving BP level less than 140/80mmHg. ResultsThe change from baseline in CD34+ subset cells (frequencies and absolute values) was not significantly different between treatment cohorts. We found a significant increase of circulating level of CD14+CD309+ cells in two patient cohorts. But more prominent change of CD14+CD309+ cells was verified in subjects who were given valsartan in high daily doses when compared with persons who were included into cohort with low daily doses of the drug (1.96% versus 2.59%, respectively; P<0.05). Therefore, both frequencies and absolute values in CD14+CD309+Tie2+ were increased significantly in patients who were treated with high doses of valsartan only. ConclusionWe found positive influence of angiotensin-2 receptor blocker valsartan in escalation doses on bone marrow-derived EPCs phenotyped as CD14+CD309+ and CD14+CD309+Tie2+ in T2DM patients with known asymptomatic CAD.

Quantifying pharmacodynamic interaction between atenolol and valsartan

Abstract We used mathematical modeling in order to determine the pharmacodynamic relationship between antihypertensive drugs atenolol and valsartan, by evaluating their effects on heart rate (HR), systolic blood pressure (SP) and diastolic blood pressure (DP). A group of twelve healthy male volunteers received a single oral dose of 100 mg of atenolol and 160 mg of valsartan, both separately and in combination. Pharmacokinetic (PK), pharmacokinetic/pharmacodynamic (PK/PD) and pharmacodynamic (PD) systems were proposed and PD model of atenolol and valsartan concentration-time profiles and PK/PD model of blood pressure and heart rate effects after administration of single doses of atenolol and valsartan and their combination were constructed. Parameters of PD system, such as gain and mean effect time, were obtained by analysis of PK and PK/PD systems. Modeling of PK and PK/PD systems and their analysis to obtain the PD results could considerably change the view o treatment of individual diseases in terms of greater knowledge of pharmacokinetics and pharmacodynamics of drugs.

Valsartan slows the progression of diabetic nephropathy in db/db mice via a reduction in podocyte injury, and renal oxidative stress and inflammation

Higher doses of AngII (angiotensin II) blockers are intended to optimize albuminuria reduction rather than for blood pressure control in chronic kidney disease. However, the long-term renoprotection of high-dose AngII blockers has yet to be defined. The present study sought to determine whether doses of ARB (AngII receptor blocker) that maximally reduce proteinuria could slow the progression of glomerulosclerosis in the uninephrectomized db/db mouse, a model of Type2 diabetes. Untreated uninephrectomized db/db mice had normal blood pressure, but developed progressive albuminuria and mesangial matrix expansion between 18 and 22weeks of age, which was associated with increased renal expression of TGFβ1 (transforming growth factor β1), PAI-1 (plasminogen-activator inhibitor-1), typeIV collagen and FN (fibronectin). Treatment with valsartan in the drinking water of db/db mice from 18 to 22weeks of age, at a dose that was determined previously to maximally reduce proteinuria, prevented the increases in albuminuria and the markers of renal fibrosis seen in untreated db/db mice. In addition, WT-1 (Wilms tumour protein-1)-immunopositive podocyte numbers were found to be lower in the untreated glomeruli of mice with diabetes. The expression of podocin and nephrin were continually decreased in mice with diabetes between 18 and 22weeks of age. These changes are indicative of podocyte injury and the administration of valsartan ameliorated them substantially. Renal expression of TNFα (tumour necrosis factor α), MCP-1 (monocyte chemoattractant protein-1), Nox2 (NADPH oxidase 2), p22phox and p47phox and urine TBARS (thiobarbituric acid-reacting substance) levels, the markers of renal inflammation and oxidative stress, were increased during disease progression in mice with diabetes. Valsartan treatment was shown to reduce these markers. Thus high doses of valsartan not only reduce albuminuria maximally, but also halt the progression of the glomerulosclerosis resulting from Type2 diabetes via a reduction in podocyte injury and renal oxidative stress and inflammation.

CHANGES IN THE PARAMETERS OF 24-HOUR BLOOD PRESSURE MONITORING AND ARTERIAL STIFFNESS IN PATIENTS WITH HYPERTENSION AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE TREATED WITH VALSARTAN

Aim. To study changes in the parameters of the 24-hour blood pressure (BP) monitoring and arterial stiffness (AS) in patients with arterial hypertension (HT) and chronic obstructive pulmonary disease (COPD) treated with angiotensin II receptors blocker, valsartan. Material and methods. Men with HT and COPD (n=23), who have been receiving valsartan with starting dose 80 mg/day for 6 months as antihypertensive therapy were included into the study. If target BP was not achieved, correction of the valsartan dose was carried out with the hydrochlorothiazide addition when needed. Clinical examination, 24-hour BP and AS monitoring using BPLab MnSDP-2 monitor ("Petr TELEGIN",Russia), clinical evaluation of COPD were performed. Results. Abnormal circadian BP profile and the elastic properties of arteries were diagnosed in the majority of hypertensive patients with COPD. Valsartan therapy allowed to achieve target BP levels in 100% of patients, normalization of circadian BP profile in 56.5%, improvement in AS parameters: a significant increase in PTT2 (from 89.6±14.3 to 94.4±18.4 ms), reduction of (dP/dt)max (from 566.6±117.9 to 518.8±146.2 mmHg/s), AIx (from -4.0±15.2 to -11.6±20.8 %) as compared to the baseline. Circadian changes in daily parameters of AS in studied patients with the most obvious night-time abnormalities of the elastic properties of arteries were detected. Valsartan intake led to Alx reduction at night-time. Conclusion. Valsartan-based therapy in hypertensive patients with concomitant COPD demonstrated a high antihypertensive efficacy and favorable changes in the elastic properties of the vascular wall that confirm its organoprotective effect.

Efficacy and safety of valsartan in hypertensive children 6 months to 5 years of age

To evaluate a dose-dependent reduction in blood pressure (BP) and overall safety of valsartan in hypertensive children. In a multicenter, randomized, double-blind, parallel-group study, 75 patients with a documented history of hypertension were randomized (2 : 1 : 2) to receive valsartan (0.25, 1 or 4 mg/kg per day) for 6 weeks, then rerandomized (1 : 1) to receive placebo or valsartan for 2 weeks. This followed the 18-week extension study in which all patients received open-label valsartan (1 mg/kg initial dose, titratable up to 4 mg/kg). The primary endpoint was the slope analysis of the dose-response curve for mean sitting SBP (MSSBP) derived through MSSBP reduction over the first 6 weeks. Safety was assessed in terms of adverse events and serious adverse events (SAEs). At Week 6, significant reductions in MSSBP (P < 0.05) from baseline were observed for all three valsartan doses. Greater reductions were observed with the medium and high doses, although the dose-response trend was not statistically significant (P = 0.099). At Week 8, a greater increase in BP was observed in patients who switched from valsartan to placebo; the difference was not significant. At the extension endpoint, MSSBP was comparable to that observed at Week 6 of the core study. Overall, valsartan was well tolerated with no dose-dependent increase in adverse events during the dose-ranging period (Week 0-6) and a comparable incidence of adverse events to placebo during the placebo withdrawal period (Week 7-8). Although a dose-response trend was observed, statistical significance was not achieved during the dose ranging (primary endpoint) or the placebo-withdrawal periods of the study. However, valsartan demonstrated significant reductions in BP compared with baseline and provided consistent reductions over 26 weeks.

Efficacy, Safety and Tolerability of High dose Valsartan Hydrochloride in Essential Hypertension

Background: Studies across the world have demonstrated the efficacy of valsartan in lowering blood pressure in a variety of patient populations, several of them investigated higher doses of the drug. This study focuses on revealing safety and efficacy of valsartan at higher doses in Bangladeshi population. Current study is planned to evaluate the efficacy, safety and tolerability of daily dose of Valsartan 160 or 320 mg in the treatment of essential hypertension. Method: This is a multi-center, open-label, observational, non-comparative, clinical decision based titration, involving about 31 centers in Bangladesh. A total of 334 newly diagnosed adult patients with essential hypertension received valsartan at a dose of 160 mg or 320 mg as deemed necessary by physician were included to allow for an assessment of efficacy, safety and tolerability. The total duration of treatment with valsartan was 16 weeks. Primary parameter for efficacy was percentage responders to valsartan at 16 weeks, reduction in Mean sitting systolic blood pressure (MSSBP) and Mean sitting Diastolic blood pressure MSDBP, control rate (% patients) achieving SBP &lt;140 mmHg and DBP &lt;90 mmHg at end point and Global assessment of efficacy and tolerability to valsartan treatment by the physician and patient. Result: Mean age of the patient was 53.31±8.8 years and 56.5% were male. A clearly evident decline is evident in mean Systolic BP and diastolic BP over the study duration. Average reduction of 30.4 ± 17.4 mmHg was seen in systolic BP, 18.4 ± 11.2 mmHg in diastolic BP and 3.5 ± 3.1/ minute in heart rate. The reduction was highly significant in both systolic BP and diastolic BP and heart rate as well (P&lt;.001). At 16 weeks only 3.4% were found to be refractory to the treatment. Global assessment of safety and efficacy was assessed on four point scale, around 30.2% of the physician rated the efficacy as excellent, around 56% rated as very good and 13.8% rated as good. Tolerability of the treatment was also assessed based on the opinion of the patient and physician concerned on four point scale. Around 34.1% of the physician rated the tolerability as excellent, around 49.7% rated as very good and 16.2% rated as good. Conclusion: Sixteen week treatment with valsartan at 160mg daily or 320 mg daily is an effective treatment for patients with essential hypertension. The drug is found to be well tolerated with minimal adverse event during the course of treatment. DOI: http://dx.doi.org/10.3329/cardio.v5i2.14323 Cardiovasc. j. 2013; 5(2): 182-189

Pharmacokinetics of Angiotensin II Receptor Blockers in the Dog Following a Single Oral Administration

Angiotensin II receptor blockers (ARBs) are effective and well-tolerated orally active anti-hypertensive agents. The purpose of this study was to investigate the pharmacokinetic properties of typical ARBs in the dog. 60 beagles were administered a single oral dose of Micardis® 80 mg (telmisartan), Cozaar® 50 mg (losartan), or Diovan® 80- and 160-mg (valsartan). The plasma concentrations of these ARBs were measured using liquid chromatography/tandem mass spectrometry and their pharmacokinetic properties were analyzed using both non-compartmental and compartmental approaches. The half-life and volume of distribution in dogs were in the order losartan>valsartan>telmisartan after oral administration. Systemic exposure was estimated by calculating the area under the plasma concentration-vs.-time curve from time zero to infinity (AUC inf ), and resulted in the order telmisartan>valsartan>losartan. The values of C max and AUC increased in proportion to the dose of valsartan. In compartmental analysis, the pharmacokinetics of telmisartan and losartan pharmacokinetics fit a 2-compartment model, while valsartan fit a 1-compartment model. These results provide detailed pharmacokinetic information of ARBs in the dog, and may aid in future development of improved formulations or fixed-dose combinations.

Efficacy of Valsartan or Valsartan combined with Zhengqingfengtongning in the treatment of IgA nephropathy with moderate proteinuria

AimTo assess the efficacy of Valsartan treatment alone or in combination with Valsartan and the Chinese traditional herbal product, Zhengqingfengtongning, for IgA nephropathy with moderate proteinuria. Materials and methodsPatients (n=156) with IgA nephropathy and moderate proteinuria (urinary protein 1–3g/24h) randomly received either combination therapy with Zhengqingfengtongning and Valsartan (intervention group, n=78), or Valsartan alone (control group, n=78). The Zhengqingfengtongning dose was 60mg, three times daily for 12 months, and the Valsartan dose was 80mg/day for 12 months. ResultsAfter 12 months of treatment, patients who received combination therapy with Zhengqingfengtongning and Valsartan showed a higher remission rate than those treated with Valsartan alone (p<0.05). The 24-h urinary protein excretion in the intervention group was significantly lower than the control group (p<0.05). No significant difference between the two groups was found in plasma albumin and total protein, serum creatinine, blood lipid levels and clinical side effects (p>0.05). ConclusionsIgA nephropathy patients with moderate proteinuria who received Zhengqingfengtongning combined with Valsartan achieved a higher remission rate than patients treated with Valsartan alone. Combination therapy was more effective in controlling 24h urinary protein compared to monotherapy, with no significant adverse effects.

ANTIHYPERTENSIVE EFFICACY AND INFLUENCE ON SEXUAL FUNCTION OF VALSARTAN AND VALSARTAN AND HYDROCHLOROTHIAZIDE COMBINATION IN SMOKERS VERSUS NON-SMOKERS WITH ARTERIAL HYPERTENSION

Aim. To study antihypertensive efficacy and safety of valsartan-based therapy as well as influence of treatment on several aspects of sexual function. Material and methods. Hypertensive patients (n=650) in 53 medical institutions of Russia were enrolled to the prospective multicenter observation study, 37.5% of smokers and 62.5% non-smokers. The evaluation of therapy efficacy was based on analysis of systolic (SBP) and diastolic (DBP) blood pressure (BP) changes. Safety and compliance of treatment was also analyzed. The evaluation of sexual function was performed with 5 universal questions selected form the International Index of Erectile Function. These ques- tions could be asked in both men and women. The valsartan dose was 80–320 mg OD. A combination of the valsartan with hydrochlorothiazide (12.5–25 mg/d), amlodipine (5–10 mg/d) or any other antihypertensive was allowed. Results. Significant similar decrease of SBP and DBP was observed in smoking and non-smoking patients (37.4/17.8 and 36.7/16.5 mm Hg respectively, р&lt;0.01 vs baseline). Differences in SBP and DBP changes were not significant between groups. Target BP level (&lt;140/90 mmHg) was reached in 81.9% smokers and 76.0% non-smokers. After 20 weeks of treatment the number of patients without sexual activity and with 1–2 successful sexual attempts in the last 4 weeks significantly decreased from 44.7 to 32.8% and from 29.1% to 23.2%, respectively (р&lt;0.05). Significant increase in the number of patients with 5–6 and 7–10 successful sexual attempts was observed (from 6.1 to 13.6% and from 3.2 to 5.9% respectively, р&lt;0.05). The treatment resulted in significant increase in the number of patients, who evaluated their sexual life satisfaction as ″very satisfied″ (from 8.2 to 14.8%, &lt;0.01). Conclusion. Comparable antihypertensive efficacy and safety were demonstrated for valsartan based therapy in smoking and non-smoking patients. During the course of treatment there was a significant improvement of sexual function and general satisfaction with sexual life in patients with arterial hypertension, which could have favorable long-term consequences in increased compliance to the antihypertensive therapy.

Targeting reduction of proteinuria in glomerulonephritis: Maximizing the antifibrotic effect of valsartan by protecting podocytes

Although angiotensin (Ang) II blockade has become a standard antifibrotic therapy in kidney disease, the therapeutic efficacy of Ang II blockade is yet to be optimized. Considering the prognostic impact of proteinuria reduction, we hypothesized that titration of Ang II blockade for optimal anti-proteinuric effect would improve renoprotection. One day after induction of Thy 1.1 glomeruonephritis, rats were treated with increasing doses of the Ang II receptor blocker valsartan in drinking water. Six days after disease induction, the therapeutic effect on proteinuria, podocyte injury and glomerular fibrosis was evaluated. Increasing doses of valsartan resulted in increasing reduction of proteinuria. The maximally effective dose of valsartan was determined to be 1000 mg/l, which reduced proteinuria by 80% and maximally reduced glomerular matrix expansion, fibronectin, collagen I and collagen III staining and glomerular mRNAs for TGFß1, PAI-1, FN and collagen I. Notably, valsartan given at this dose prevented podocyte dysfunction by preserving expression of podocin and nephrin and the counter-regulating molecule B7-1 that is involved in podocyte injury. These results support the hypothesis that higher doses of valsartan are required to optimize proteinuria reduction and glomerulosclerosis amelioration. Further, the optimal dose of valsartan also provides an additional therapeutic effect by preventing podocyte dysfunction.

Aliskiren reduces home blood pressure and albuminuria in patients with hypertensive nephrosclerosis

The aim of this study was to investigate the antialbuminuric and antihypertensive effects of aliskiren by monitoring home blood pressure (BP) in comparison with the effects of the angiotensin receptor blocker (ARB) valsartan in patients with hypertensive nephrosclerosis and albuminuria. We conducted an open-label, randomized trial to compare the effects of aliskiren with those of valsartan. Patients with BP <150/90mmHg, an estimated glomerular filtration rate of 90-30mL/min/1.73m(2), and albuminuria >30mg/g, despite treatment with a 160mg daily dose of valsartan, were randomly assigned to the following two groups: the aliskiren group, who switched from 160mg/day valsartan to 150mg/day aliskiren, which was later increased to 300mg/day (n=20); and the valsartan group, who continued with 160mg/day valsartan (n=20). After 12weeks of treatment, although there was no significant difference in clinic BP between groups, a significant reduction in morning and evening systolic BP was observed in the aliskiren group. The decrease in albuminuria in the aliskiren group was significantly better than that in the valsartan group, and a significant correlation was noted between the change in morning systolic BP and the change in albuminuria in the aliskiren group (r=0.564, P=0.0084). We showed that aliskiren treatment leads to a greater reduction in albuminuria and home systolic BP values than valsartan in patients with nephrosclerosis. We propose that aliskiren therapy should be considered as a therapeutic modality to complement ARBs in hypertensive patients with nephrosclerosis.