Valsartan Therapy Research Articles

Fixed-dose combination therapy of nebivolol and valsartan for the treatment of hypertension

ABSTRACTRecent large clinical trials have refuted earlier suggestions from the Joint National Committee 8 committee that less aggressive targets for blood pressure control were all that could be justified in most hypertensive patients. It now does appear that in fact “lower is better,” with blood pressure targets < 120/80 mm Hg appropriate for many hypertensive patients. Two drug combinations are often indicated as initial therapy if a 20/10 mm Hg or greater blood pressure reduction is necessary to reach target. Combinations consisting of β-blockers and renin-angiotensin-aldosterone system inhibitors have previously been deemed “less effective,” based on partially overlapping mechanisms of action and limited clinical trial evidence. Nebivolol is a vasodilating β1-selective blocker and β3- adrenoceptor agonist; β3-adrenoceptor activation increases nitric oxide concentrations and thus explains the vasodilatory effect. A recent 8-week randomized trial (N=4,161) in individuals with stage 1-2 hypertension demonstrated that single-pill fixed dose combinations (FDC) of nebivolol and valsartan, an angiotensin II subtype 1 receptor blocker, were more effective in reducing blood pressure than the corresponding monotherapies, with comparable tolerability. In addition, an ABPM-biomarkers substudy from that trial (n=805) demonstrated that the FDC prevented a valsartan-induced increase in plasma renin activity, and that the nebivolol/valsartan 20/320 mg/day dose reduced plasma aldosterone concentration significantly more than valsartan 320 mg/day. This article will describe the properties of nebivolol that make it unique and separate it from other β-blockers, and will further support the pharmacological advantages of this particular combination.

Effect of low-dose valsartan on proteinuria in normotensive immunoglobulin A nephropathy with minimal proteinuria: a randomized trial.

Background/Aims:Immunoglobulin A nephropathy (IgAN) is a generally progressive disease, even in patients with favorable prognostic features. In this study, we aimed to investigate the antiproteinuric effect and tolerability of low-dose valsartan (an angiotensin II receptor blocker) therapy in normotensive IgAN patients with minimal proteinuria of less than 0.5 to 1.0 g/day.Methods:Normotensive IgAN patients, who had persistent proteinuria with a spot urine protein-to-creatinine ratio of 0.3 to 1.0 mg/mg creatinine, were recruited from five hospitals and randomly assigned to either 40 mg of valsartan as the low-dose group or 80 mg of valsartan as the regular-dose group. Clinical and laboratory data were collected at baseline, and at 4, 8, 12, and 24 weeks after valsartan therapy.Results:Forty-three patients (low-dose group, n = 23; regular-dose group, n = 20) were enrolled in the study. Proteinuria decreased significantly not only in the regular-dose group but also in the low-dose group. The change in urine protein-to-creatinine ratio at week 24 was −41.3% ± 26.1% (p < 0.001) in the regular-dose group and −21.1% ± 45.1% (p = 0.005) in the low-dose group. In the low-dose group, blood pressure was constant throughout the study period, and there was no symptomatic hypotension. In the regular-dose group, blood pressure decreased at weeks 8 and 12. No significant change in glomerular filtration rate, serum creatinine level, or serum potassium level was observed during the study period.Conclusions:Our results suggest that low-dose valsartan can significantly reduce proteinuria without causing any intolerability in normotensive IgAN patients with minimal proteinuria.

To compare anti-albumin urea effects of valsartan alone with combination of valsartan and amlodipine in patients of chronic kidney disease.

Objective:To compare anti-albumin urea effects of Valsartan alone with combination of Valsartan and Amlodipine in patients of chronic kidney disease.Methods:This randomized clinical trial was conducted at the Department of Medicine, Combined Military Hospital Bahawalpur, from April 2014 to 30 September 2014. 140 patients of chronic kidney disease with baseline blood pressure more than 140/90mm Hg having raised urinary albumin: creatinine ratio (UACR). UACR more than 3.5 mg/mmol was considered abnormal. Group-A was treated with Valsartan 80mg daily and Group-B was treated with valsartan 80 and amlodipine 10mg once a day. We did not change the dose of drugs and check spot UACR at base line and after six months with therapy and compare improvement in UACR between Group-A and B. Data was analyzed by statistical software packages (SPSS 16.0).Results:In both the groups, BP was significantly lower than the respective value. Mean decrease in spot UACR in Group-A was 3.18±2.64 mg/mmol and UACR in Group-B mean decrease in UACR was 13.01±20.11 mg/mmol. P value was< 0.05. Conclusion:The combination therapy of valsartan with amlodipine significantly lowers the albuminuria in chronic Kidney disease and reduce the progression of disease as compared to Valsartan alone therapy.

Effect of aliskiren on vascular remodelling in small retinal circulation

In hypertension, changes in small arterial structure are characterized by an increased wall-to-lumen ratio (WLR). These adaptive processes are modulated by the rennin-angiotensin system. It is unclear whether direct renin inhibitors exert protective effects on small arteries in hypertensive patients. In this double-blind, randomized, placebo-controlled study (http://www.clinicaltrials.gov: NCT01318395), 114 patients with primary hypertension were randomized to additional therapy with either placebo or aliskiren 300 mg for 8 weeks after 4 weeks of standardized open-label treatment with valsartan 320 mg (run-in phase). Parameter of arteriolar remodelling was WLR of retinal arterioles (80 - 140 μm) assessed noninvasively and in vivo by scanning laser Doppler flowmetry (Heidelberg Engineering, Germany). In addition, pulse wave analysis (SphygmoCor, AtCor Medical, Australia) and pulse pressure (PP) amplification were determined. In the whole study population, no clear effect of additional therapy with aliskiren on vascular parameters was documented. When analyses were restricted to patients with vascular remodelling, defined by a median of WLR more than 0.3326 (n = 57), WLR was reduced after 8 weeks by the treatment with aliskiren compared with placebo (-0.044 ± 0.07 versus 0.0043 ± 0.07, P = 0.015). Consistently, after 8 weeks of on-top treatment with aliskiren, there was an improvement of PP amplification compared with placebo (0.025 ± 0.07 versus -0.034 ± 0.08, P = 0.013), indicative of less stiff arteries in the peripheral circulation. Thus, our data indicate that treatment with aliskiren, given on top of valsartan therapy, improves altered vascular remodelling in hypertensive patients.

Evaluation of Anti-Ischemic and Cardioprotective Effects of Nicorandil in Patients With Stable Angina

The aim of our study was to assess the anti-ischemic and cardiouprotective efficiency of the activator of potassium channels nicorandil in patients with stable angina during long-term intake on the background of standard therapy of coronary heart disease (CHD), including aspirin, rosuvastatin, valsartan and bisoprolol in comparison with standard therapy and long-acting form of nitrates. We compared the dynamics of nitroglycerine consumption, frequency of angina attacks, carried veloergometry, daily monitoring of an electrocardiogram by Holter, echocardiography, assess the state of lipid and carbohydrate metabolism, were determined concentrations of certain markers of systemic inflammation. The results showed that the inclusion of nicorandil into the standard therapy CHD leads to more significant changes in indicators of clinical evaluation of angina pectoris, myocardial remodeling, inflammatory markers.

Renal effects of the angiotensin receptor neprilysin inhibitor LCZ696 in patients with heart failure and preserved ejection fraction.

Increases in serum creatinine with renin-angiotensin-aldosterone system (RAAS) inhibitors can lead to unnecessary discontinuation of these agents. The dual-acting angiotensin receptor neprilysin inhibitor LCZ696 improves clinical outcome patients with heart failure with reduced ejection fraction, and pilot data suggest potential benefit in heart failure with preserved ejection fraction (HFpEF). The effects of LCZ696 on renal function have not been assessed. A total of 301 HFpEF patients were randomly assigned to LCZ696 or valsartan in the PARAMOUNT trial. We studied renal function [creatinine, estimated glomerular filtration rate (eGFR), cystatin C, and urinary albumin to creatinine ratio (UACR)] at baseline, 12 weeks, and after 36 weeks of treatment. Worsening renal function (WRF) was determined as an serum creatinine increase of >0.3 mg/dL and/or >25% between two time-points. Mean eGFR at baseline was 65.4 ± 20.4 mL/min per 1.73 m(2) . The eGFR declined less in the LCZ696 group than in the valsartan group (-1.5 vs. -5.2 mL/min per 1.73 m(2) ; P = 0.002). The incidence of WRF was lower in the LCZ696 group (12%) than in the valsartan group (18%) at any time-point, but this difference was not statistically significant (P = 0.18). Over 36 weeks, the geometric mean of UACR increased in the LCZ696 group (2.4-2.9 mg/mmol), whereas it remained stable in the valsartan group (2.1-2.0 mg/mmol; P for difference between groups = 0.016). In patients with HFpEF, therapy with LCZ696 for 36 weeks was associated with preservation of eGFR compared with valsartan therapy, but an increase in UACR.

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.

Protective effects of aliskiren and valsartan in mice with diabetic nephropathy.

We investigated whether aliskiren, a direct renin inhibitor, provided protection in a model of diabetic nephropathy in mice and compared its protective effects to valsartan, an angiotensin II type 1 receptor blocker. Hyperglycemia was induced with streptozotocin (STZ, 40 mg/kg/day × 5 days) injection in DBA/2J mice fed on a high fat diet. Mice were treated with either aliskiren (25 mg/kg/day) or valsartan (8 mg/kg/day) for 6 weeks. Aliskiren and/or valsartan treatment significantly attenuated albuminuria, urinary nephrin excretion and glomerulosclerosis. Aliskiren and/or valsartan prevented reduction of podocin and WT1 protein abundance in diabetic mice. Aliskiren and/or valsartan significantly prevented increased expression of profibrotic growth factors (TGFβ, CTGF and PAI-1), proinflammatory cytokines (MCP-1, TNFα and IL-1β), endoplasmic reticulum (ER) stress markers (CHOP and XBP-1) and lipid accumulation in the kidney of diabetic animals. Aliskiren showed similar efficacy compared to valsartan therapy and dual treatment in some aspects has synergistic protective effects. Our study indicates that aliskiren and/or valsartan protects against diabetic kidney disease through multiple mechanisms, including decreasing podocyte injury, activation of profibrotic growth factors and proinflammatory cytokines, ER stress and accumulation of lipids.

Effect of Add‐on Aliskiren to Type 1 Angiotensin Receptor Blocker Therapy on Endothelial Function and Autonomic Nervous System in Hypertensive Patients With Ischemic Heart Disease

The aim of this study was to evaluate the add-on effect of aliskiren to valsartan on endothelial-dependent vasodilation in hypertensive patients with ischemic heart disease (IHD). After 4 weeks of treatment with 80 mg of valsartan, 28 patients were allocated to either continued treatment with valsartan or an add-on treatment with valsartan plus 150 mg of aliskiren. Aliskiren significantly decreased plasma renin activity, whereas endothelium-dependent vasodilation measured by flow-mediated dilation (FMD) did not change. In contrast, heart rate significantly decreased (73.1 ± 9.8 to 66.3 ± 7.0 beats per minute at baseline and 24 weeks, respectively [P = .009]) and the standard deviation of the R-R intervals (SDNN) significantly increased in the aliskiren group. The add-on aliskiren to valsartan therapy may not improve endothelial functions, although it significantly reduced resting heart rate via regulation of the autonomic nervous system in hypertensive patients with IHD.

Valsartan-induced Acute Pancreatitis

Gastrointestinal toxicity is uncommon among patients treated with angiotensin II receptor antagonists. A 58-year-old man presented with nausea, vomiting and constant pain in the epigastrium that radiated to the flanks. He received treatment with valsartan (160 mg daily) for hypertension. The clinical, biochemical and radiological findings were compatible with a diagnosis of acute pancreatitis. After the patient achieved a clinical and biochemical recovery, the valsartan therapy was started again. Six weeks later, he returned to the hospital with an attack of pancreatitis. Subsequently, he returned with repeated attacks of pancreatitis twice, and the valsartan was discontinued. Ten months after the treatment, the patient had no complaints. When severe abdominal symptoms occur for no apparent reason during treatment with valsartan, a diagnosis of pancreatitis should be considered.

VALSARTAN TO ATTENUATE RENAL DAMAGE IN UNILATERAL URETERAL OBSTRUCTION

Objective: This experimental study aims to observe the effect of valsartan to attenuate renal damage in unilateral ureteral obstruction. Material &amp; method: Experimental study was performed using 30 wistar rats with unilateral ureteral obstruction achieved by ligation of the left ureter. Rats were divided into two groups, no treatment group and valsartan group. At the 14th day, evaluation was performed to compare interstitial fibrosis, hydropic degeneration, and tubular atrophy between the two groups using haematoxylin-eosin staining. Only rats surviving until at least the 7th day are included in the study. Results: From thirteen wistar rats in no treatment group, there were two with moderate interstitial fibrosis and eleven with mild interstitial fibrosis while all rats in valsartan group had mild interstitial fibrosis (p &gt; 0.05). There is no significant difference on hydropic degeneration between no treatment and valsartan group (31.46 vs 33.67; p &gt; 0.05). There is also no significant difference in tubular atrophy between the two groups (61.78 vs 62.07; p &gt; 0.05). Conclusion: Valsartan therapy in antihypertensive dosage has no significant effect in to attenuate interstitial fibrosis, hydropic degeneration, and tubular atrophy in unilateral ureteral obstruction in wistar rats. Keywords: Unilateral ureteral obstruction, valsartan, interstitial fibrosis.

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.

Combination Pravastatin and Valsartan Treatment Has Additive Beneficial Effects to Simultaneously Improve Both Metabolic and Cardiovascular Phenotypes Beyond That of Monotherapy With Either Drug in Patients With Primary Hypercholesterolemia

Statin and angiotensin II type 1 receptor blocker therapy improves endothelial dysfunction using distinct mechanisms. We evaluated simultaneous vascular and metabolic responses to pravastatin and valsartan therapy, alone or in combination, in hypercholesterolemic patients. Forty-eight hypercholesterolemic patients (23 had metabolic syndrome) were given pravastatin 40 mg and placebo, pravastatin 40 mg and valsartan 160 mg, or valsartan 160 mg and placebo daily during each 2-month treatment period in a randomized, single-blind, placebo-controlled, crossover trial with three treatment arms and two washout periods (each 2 months). Brachial artery flow-mediated dilation and C-reactive protein improved to a greater extent with combined therapy compared with either monotherapy. Importantly, we also observed simultaneous improvement in metabolic phenotypes, with all three treatments causing increased plasma adiponectin levels, reduced fasting insulin levels, and increased insulin sensitivity relative to baseline measurements. For the first time in a statin combination trial, pravastatin combined with valsartan therapy increased plasma adiponectin, lowered fasting insulin levels, and improved insulin sensitivity in an additive manner when compared with monotherapy alone. In contrast to other statins, hydrophilic pavastatin may be combined with other drugs to safely reach lipid target levels while simultaneously improving the metabolic and cardiovascular phenotype of patients at high risk.

A meta-analysis of randomized trials of telmisartan versus losartan for reduction of ambulatory blood pressure

A previous meta-analysis of a few randomized controlled trials (RCTs) suggests a significant reduction in ambulatory blood pressure (BP) with telmisartan as compared with losartan monotherapy. We performed an updated meta-analysis of RCTs of telmisartan versus losartan therapy for reduction of ambulatory BP in patients with hypertension. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through July 2012 using PubMed and OVID. Eligible studies were RCTs of telmisartan versus valsartan therapy enrolling individuals with hypertension and reporting ambulatory BP as an outcome. For each study, data regarding changes from baseline in ambulatory (24 h, last 6 h, morning, daytime and nighttime) BP in both the telmisartan and losartan groups were used to generate mean differences (MDs) and 95% confidence intervals (CIs). Of 34 potentially relevant articles screened initially, 9 reports of RCTs enrolling a total of 2409 patients with hypertension were identified and included. Pooled analysis suggested significant reductions in all of 24-h (MD of systolic/diastolic BP, -2.09/-1.57 mm Hg; 95% CI, -3.39/-2.32 to -0.79/-0.82 mm Hg), last 6-h (-2.96/-2.15 mm Hg; -3.80/-2.72 to -2.13/-1.59 mm Hg), morning (-2.71/-2.37 mm Hg; -3.73/-3.33 to -1.69/-1.41 mm Hg), daytime (-1.74/-1.73 mm Hg; -3.27/-2.84 to -0.20/-0.62 mm Hg) and nighttime BP (-2.70/-2.08 mm Hg; -4.07/-3.24 to -1.33/-0.92 mm Hg) among patients randomized to telmisartan versus losartan therapy. In conclusion, telmisartan therapy appears to reduce ambulatory BP more than losartan therapy in patients with hypertension.

ASSA13-16-4 The Influence of Combination of Amlodipine and Valsartan on Plasma Free Fat Acid and Adiponectin in Patients with Essential Hypertension

<h3>Objective</h3> To investigate the influence of combination therapy of amlodipine and valsartanon on the plasma adiponectin (ADPN) and free fatty acids (FFAs) levels in patients with essential hypertension. <h3>Methods</h3> Fifty hypertensive patients were included. After 4 week amlodipine (5mg/d) treatment, 34 patients with diastolic blood pressure (DBP) equal to or more than 90 mmHg were included in the double blind period and randomly divided into amlodipine (amlodipine, 5mg/d) and the combination (amlodipine 5mg + valsartan 80 mg/d) groups for other 8 weeks. BP, blood lipids, blood glucose, ADPN and FFA were measured at baseline, 4 and 12 week after treatment. Eighteen normotensive adults were selected as the control. <h3>Results</h3> At baseline, FFA, total cholesterol (TC) and triglycerides (TG) were significantly higher, but ADPN lower in the hypertensive group than in the control group. Four weeks amlodipine treatment increased significantly ADPN levels (4.75 ± 1.88 vs 5.09 ± 1.97 mg/L, P. <h3>Conclusions</h3> Four weeks amlodipine monotherapy can significantly increase the plasma ADPN level. On this base, the combination therapy of amlodipine and valsartan can better improve plasma ADPN and FFA than amlodipine monotherapy.

A meta-analysis of randomized trials of telmisartan vs. valsartan therapy for blood pressure reduction

A previous meta-analysis of six randomized head-to-head trials suggests that the blood pressure (BP)-lowering capabilities of telmisartan may be comparable to those of valsartan. We performed an updated meta-analysis of telmisartan vs. valsartan therapy for the reduction of BP in hypertensive patients. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through August 2012 using web-based search engines (PubMed, OVID). Eligible studies were prospective randomized controlled trials examining telmisartan vs. valsartan therapy and reporting clinic BP as an outcome. For each study, the data regarding changes from baseline to final clinic systolic BP (SBP) and diastolic BP (DBP) in both the telmisartan and valsartan groups were used to generate mean differences (MDs) and 95% confidence intervals (CIs). Of the 62 potentially relevant articles initially screened, 17 reports about prospective randomized controlled clinical trials of telmisartan vs. valsartan therapy, including a total of 5422 patients with hypertension, were identified and included. Pooled analysis suggested significant differences in BP reductions among the patients randomized to telmisartan vs. valsartan therapy (MD for SBP, -2.04 mm Hg; 95% CI, -2.80 to -1.28 mm Hg; P<0.00001; MD for DBP, -1.08 mm Hg; 95% CI, -1.55 to -0.62 mm Hg; P<0.00001). When data from the monotherapy and combination therapy (with hydrochlorothiazide) trials were pooled separately, telmisartan therapy was associated with a statistically significant difference in BP reductions relative to valsartan therapy in both the monotherapy and combination therapy groups. In conclusion, telmisartan therapy appears to reduce BP more than valsartan therapy in patients with hypertension.

Effect of Valsartan on Systemic Right Ventricular Function

Background— The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated. Methods and Results— We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared with placebo in patients with a systemic right ventricle caused by congenitally or surgically corrected transposition of the great arteries. The primary end point was change in right ventricular ejection fraction during 3-year follow-up, determined by cardiovascular magnetic resonance imaging or, in patients with contraindication for magnetic resonance imaging, multirow detector computed tomography. Secondary end points were change in right ventricular volumes and mass, peak, and quality of life. Primary analyses were performed on an intention-to-treat basis. A total of 88 patients (valsartan, n=44; placebo, n=44) were enrolled in the trial. No serious adverse effects occurred in either group. There was no significant effect of 3-year valsartan therapy on systemic right ventricular ejection fraction (treatment effect, 1.3%; 95% confidence interval, −1.3% to 3.9%; P =0.34), maximum exercise capacity, or quality of life. There was a larger increase in right ventricular end-diastolic volume (15 mL; 95% confidence interval, 3–28 mL; P &lt;0.01) and mass (8 g; 95% confidence interval, 2–14 g; P =0.01) in the placebo group than in the valsartan group. Conclusions— There was no significant treatment effect of valsartan on right ventricular ejection fraction, exercise capacity, or quality of life. Valsartan was associated with a similar frequency of significant clinical events as placebo. Small but significant differences between valsartan and placebo were present for change in right ventricular volumes and mass. Clinical Trial Registration— URL: http://www.controlled-trials.com . Unique identifier: ISRCTN52352170.

Relationship between the receptor occupancy profile and pleiotropic effects of angiotensin II receptor blockers

To investigate whether (i) angiotensin receptor occupying profiles of angiotensin II receptor blockers (ARBs) vary among the drugs and (ii) such differences contribute to the degree of their pleiotropic effects. In a randomized, three phase crossover study, nine hypertensive patients received repeated doses (each recommended starting dose for 7 days and then each maximum recommended dose for 20 days) of irbesartan, valsartan and candesartan. The time course profiles and trough level of receptor occupancy were determined on days 7 and 28, respectively. The pleiotropic effect related parameters were measured on days 0 and 28 in each trial. Of the pleiotropic effect related parameters investigated, urinary 8-isoprostane, fasting serum insulin and homeostasis model assessment of insulin resistance index were more suppressed after 4 weeks treatment with irbesartan than after candesartan and valsartan therapy, respectively. The maximum, area under the curve and trough values of receptor occupancy significantly differed between the ARBs [geometric mean (and 95% CI) of trough value 18.1 (12.9, 25.3) for irbesartan, 9.6 (6.0, 15.3) for valsartan and 5.5 (2.8, 10.8) for candesartan, respectively] and were negatively correlated with the change in urinary 8-isoprostane (r = -0.46 - -0.55, P < 0.05), but not the markers of insulin resistance (r = 0.02-0.15, P = 0.46-0.94). Our results demonstrate that the receptor occupying profiles are different among the ARBs. This class of drugs might have both receptor occupancy dependent and independent pleiotropic effects.

Oxidant / antioxidant status and thyroid function tests in hypertensive patients treated by captopril or valsartan

Objectives: To assess, the oxidant / antioxidant status and thyroid function tests in newly diagnosed hypertensive patients and the effect of therapy with captopril or valsartan for 2 months on these parameters in comparison to healthy control subjects. Methods: This study was conducted in Ibn-Sina Teaching Hospital, Consultative Clinic for Internal Medicine in Mosul city, from Jan. to Dec. 2008. Patients with certain criteria were included in this study. Blood samples were taken from the patients and assay of serum level of malondialdehyde (MDA), total antioxidant status (TAS) and thyroid hormones; [total triiodothyronine (T3), total thyroxine (T4) and thyroid stimulating hormone (TSH)] were done. They then started to receive either valsartan in the first group or captopril in the second group for 2 months after which another set of blood samples were taken and assayed for the same parameters mentioned above, were done. Forty apparently healthy subjects were also included in this study. They were recruited as a control group. Results: Before starting therapy newly diagnosed hypertensive patients, had a significantly higher MDA serum levels and a significantly lower TAS, with non-significant differences in the levels of thyroid hormones (TT3, TT4 & TSH) in comparison to healthy controls. After 2 months of treatment with either captopril or valsartan, there was a significant decrease in MDA serum levels and a significant increase in TAS levels with non-significant effects on thyroid hormonal levels in comparison to pre-therapy stage. Conclusion: Captopril and valsartan therapy improves oxidant / antioxidant status and carry no adverse effects on thyroid function in newly diagnosed patients with mild to moderate hypertension.

Chrono-medical impact on morning hypertension therapy and home blood pressure measurement: The Val-HOPE study

We evaluated chrono-medically the effect of valsartan's therapy on home-measured blood pressure (BP) in patients, whose blood pressure was inadequately controlled with or without anti-hypertensive agents. The subjects were 42 men and 63 women, of average age of 63.4years. Administration of valsartan significantly reduced blood pressure both at the clinic and at home, i.e., from 158.6±13.7/90.9±11.6 to 139.3±12.9/82.5±10.2mmHg, and from 150.0±11.6/89.4±10.9 to 136.6±11.9/82.5±10.2mmHg (p<0.001), respectively.