Dose Of Valsartan Research Articles

Effect of Valsartan With Bedtime Dosing on Chronic Kidney Disease Patients With Nondipping Blood Pressure Pattern

Nondipping blood pressure (BP) pattern is a potential independent risk factor for chronic kidney disease (CKD). Bedtime administration of valsartan is considered to normalize circadian rhythm and protect the kidneys and heart in CKD patients. However, more clinical trials are needed to confirm this benefit. Sixty patients with nondipping BP pattern and thirty patients with dipping BP pattern were enrolled in this study, and the patients with nondipping BP pattern were randomly divided into two groups and treated with bedtime or awakening doses of valsartan (80-320 mg). Nondipping BP patients treated with bedtime doses of valsartan showed a greater reduction in 24-hour proteinuria and bedtime proteinuria, a greater delayed decline in estimated glomerular filtration rate, and more protection against myocardial hypertrophy (P<.05) compared with patients with the nondipping BP pattern treated with the awakening dose (P<.05). This was similar to patients with dipping BP. No severe clinical complications were recorded in these patients. Valsartan with bedtime dosing in CKD patients with the nondipping BP pattern have better renal and cardiovascular protection. Antihypertensive "chronotherapy" may be useful in clinical practice for CKD patients.

Lithium Toxicity and Neurologic Effects: Probable Neuroleptic Malignant Syndrome Resulting from Lithium Toxicity

Introduction. We present the case of a patient who developed lithium toxicity with normal therapeutic levels, as a result of pharmacokinetic interaction with Valsartan, and probable Neuroleptic Malignant Syndrome from the ensuing lithium toxicity. Case Presentation. A 59-year old black male with bipolar disorder maintained on lithium and fluphenazine therapy presented with a 2 week history of worsening confusion, tremor, and gait abnormality. He recently had his dose of Valsartan increased. At presentation, patient had signs of autonomic instability, he was confused, dehydrated, and had rigidity of upper extremities. Significant labs on admission were lithium level-1.2, elevated CK-6008, leukocytosis WBC-22, and renal impairment; Creatinine-4.1, BUN-35, HCO3-20.1, and blood glucose 145. CT/MRI brain showed old cerebral infarcts, and there was no evidence of an infective process. Lithium and fluphenazine were discontinued, his lithium levels gradually decreased, and he improved with supportive treatment including rehydration and correction of electrolyte imbalance. Conclusions. This case illustrates that lithium toxicity can occur within therapeutic levels, and the neurotoxic effect of lithium can include Neuroleptic Malignant Syndrome. Clinicians should be aware of the risk associated with drug interactions with lithium.

The impact of dose of the angiotensin-receptor blocker valsartan on the post-myocardial infarction ventricular remodeling: study protocol for a randomized controlled trial.

BackgroundAngiotensin-converting enzyme inhibitors and the angiotensin-receptor blocker valsartan ameliorate ventricular remodeling after myocardial infarction (MI). Based on previous clinical trials, a maximum clinical dose is recommended in practical guidelines. Yet, has not been clearly demonstrated whether the recommended dose is more efficacious compared to the lower dose that is commonly used in clinical practice.Method/DesignValsartan in post-MI remodeling (VALID) is a randomized, open-label, single-blinded multicenter study designed to compare the efficacy of different clinical dose of valsartan on the post-MI ventricular remodeling. This study also aims to assess neurohormone change and clinical parameters of patients during the post-infarct period. A total of 1116 patients with left ventricular dysfunction following the first episode of acute ST-elevation MI are to be enrolled and randomized to a maximal tolerable dose (up to 320 mg/day) or usual dose (80 mg/day) of valsartan for 12 months in 2:1 ratio. Echocardiographic analysis for quantifying post-MI ventricular remodeling is to be conducted in central core laboratory. Clinical assessment and laboratory test are performed at fixed times.DiscussionVALID is a multicenter collaborative study to evaluate the impact of dose of valsartan on the post-MI ventricular remodeling. The results of the study provide information about optimal dosing of the drug in the management of patients after MI. The results will be available by 2012.Trial registrationNCT01340326

Varying patterns of the antihypertensive and antialbuminuric response to higher doses of renin–angiotensin–aldosterone system blockade in albuminuric hypertensive type 2 diabetes mellitus patients

In patients with type 2 diabetes mellitus (T2DM), blocking of the renin-angiotensin-aldosterone system (RAAS) has demonstrated efficacy in lowering blood pressure (BP) and urinary albumin excretion rate (UAER). Nonetheless, not all patients successfully respond to RAAS blockade with a reduction in BP and UAER. This secondary analysis of a double-blind study of 391 patients with T2DM assessed the importance of using higher doses of the RAAS blocker valsartan to improve the BP and UAER response in patients initially identified as prompt or delayed responders. All patients received a starting dose of valsartan 160 mg for a 4-week run-in period to classify them as either prompt responders (SBP < 130 mmHg or reduction in SBP ≥10 mmHg, 53%) or delayed responders (47%). All patients were then subsequently randomized to one of three valsartan doses: 160, 320, or 640 mg/day for 26 weeks. Higher doses of valsartan (640 mg) demonstrated additional reductions in SBP among the prompt responders and led to greater SBP reductions from baseline (19.8 mmHg) compared with valsartan 160 (14.4 mmHg, P < 0.05) and 320 mg (16.5 mmHg). Among delayed responders, SBP reductions from baseline to end of study were similar (11-14 mmHg, P > 0.05) across all valsartan doses. For UAER, higher valsartan doses produced further reductions by week 30, regardless of initial response. Higher doses of valsartan did not appear to recruit delayed responders, but enhanced the prompt responder effects in patients with T2DM. Not all patients successfully respond in concordance to RAAS blockade with both reductions in BP and UAER. Reduction in BP dominates the antialbuminuric effect in both valsartan prompt responders and delayed responders independent of dose.

Valsartan decreases TGF-β1 production and protects against chlorhexidine digluconate-induced liver peritoneal fibrosis in rats

Peritoneal fibrosis (PF) is a recognized complication of long-term peritoneal dialysis (PD) and can lead to ultrafiltration failure. The present study was designed to investigate the protective effects of valsartan on chlorhexidine digluconate-induced PF by decreasing TGF-β1 production in rats. PF was induced in Sprague–Dawley rats by daily administration of 0.5 ml 0.1% chlorhexidine digluconate in normal saline via peritoneal dialysis (PD) tube for 1 week. Rats received daily intravenous injections of low dose valsartan (1 mg/kg) or high dose valsartan (3 mg/kg) for 1 week. After 7 days, conventional 4.25% Dianeal (30 ml) was administered via a PD catheter with a dwell time of 4 h and assessed of peritoneal function. At the end of dialysis, rats were sacrificed and the liver peritoneum was harvested for microscopically and immunohistochemistry. There was no significant difference in mean arterial pressure and heart rate between groups. After 4 h of PD, the D 4/P 4Urea level was reduced, the D 4/D 0 glucose level, serum and dialysate transforming growth factor-β1 (TGF-β1) level was increased, the liver peritoneum was markedly thicker, and the expression of TGF-β1, alpha-smooth muscle actin (α-SMA), fibronectin, collagen, and vascular endothelial growth factor (VEGF) were elevated in the PF group compared with the vehicle group. High dose of valsartan decreased the serum and dialysate TGF-β1 level, decreased the thickness of the liver peritoneum, and decreased the expression of TGF-β1, α-SMA, fibronectin, collagen, and VEGF-positive cells in liver peritoneum. The low dose of valsartan did not protect against chlorhexidine digluconate-induced PF in rat. Valsartan protected against chlorhexidine digluconate-induced PF in rats by decreasing TGF-β1 production.

E0349 Clinical observation on different dosage of valsartan in treatment of heart failure

ObjectiveTo explore the clinical value of different dosage of valsartan in treatment of chronic heartfailure (CHF).Methods99 patient s with CHF were randomly divided into three groups: benazepril group (group A,...

Effectiveness and safety of high-dose valsartan monotherapy in hypertension treatment: the ValTop study

Early combination therapy is increasingly recommended in hypertension management because of increased risk of adverse effects with high-dose monotherapy. However, this risk is not necessarily increased for high doses of angiotensin receptor blockers (ARB). ValTop study compared efficacy and safety of high vs. conventional dose of valsartan in hypertensive patients. ValTop was a controlled, randomized, double-blind trial. Of 6035 screened subjects, 4004 mild-to-moderate hypertensive patients (mean seated diastolic blood pressure (MSDBP) 90-109 mm Hg) started 4-week open-label treatment with valsartan 160 mg. Of them, 3776 were randomized to receive valsartan 160 mg (N=1900) or 320 mg (N=1876) o.d. for 4 weeks. In 28-week open-label extension study, all participating patients (N=642) received valsartan 320 mg. Valsartan 160 mg reduced MSDBP by 10.0 mm Hg in the initial open-label phase. Further BP reductions in the double-blind phase were significantly (P<0.0001) greater in the 320 mg group than in the 160 mg group for MSDBP (1.6 ± 0.18 mm Hg vs. 0.5 ± 0.18 mm Hg) and mean seated systolic BP (3.3 ± 0.31 mm Hg vs. 0.7 ± 0.31 mm Hg). The size of the additional effect of the 320 mg dose on BP was similar in subjects controlled or not by the initial 160 mg dose. Adverse event (AE) rates were similar in both treatment groups, drug-related AEs occurring in <5% of subjects in each phase. High-dose valsartan is safe and effective in uncomplicated mild-to-moderate hypertension independently of the initial response to a moderate dose. High-dose ARB monotherapy may thus be a viable option in hypertension management.

Is the reno-protective effect of valsartan dose dependent? A comparative study of 80 and 160 mg day−1

Whether the reno-protective effect of angiotensin receptor blockers is dose dependent is unknown for the Japanese population. We sought to elucidate the dose-dependent reno-protective effects of valsartan in Japanese hypertensive patients with albuminuria. This was a multi-center, open-label, parallel-group trial. A total of 181 patients were randomized to receive either 80 (n=89) or 160 mg day(-1) (n=92) of valsartan for 24 weeks. Then, the effects on blood pressure, urinary albumin excretion (UAE), type IV collagen and beta(2)-microglobulin (beta2MG) were determined. Systolic and diastolic blood pressures decreased substantially by almost the same extent in the low-dose and high-dose groups, showing no inter-group difference during the treatment. The UAE value decreased significantly by 35% in both groups. Urinary excretion of beta2MG was significantly decreased in the high-dose group (17%), but not in the low-dose group (13%), although the decrease was not significantly different between the two groups (P=0.74). Urinary excretion of type IV collagen decreased non-significantly by 10% in the low-dose group and by 8% in the high-dose group, showing no significant inter-group difference (P=0.78). Low (80 mg day(-1)) and high (160 mg day(-1)) doses of valsartan showed a similar effect of lowering blood pressure. The high dose of valsartan resulted in a slightly greater decrease in urinary beta2MG, but it was inconclusive whether the high dose was more reno-protective as compared with the low dose.

Comparison of once-daily versus twice-daily dosing of valsartan in patients with chronic stable heart failure

The safety of once-daily (qd) dosing of valsartan in heart failure (HF) patients is not known. This 10-week, double-blind trial examined the relative safety and efficacy of valsartan administered qd versus twice-daily (bid). HF patients (NYHA class II-III) receiving diuretics (87%), angiotensin-converting enzyme inhibitors (98%), beta-blockers (92%), aldosterone antagonists (25%), or digoxin (32%) were randomized to valsartan 40 mg bid (n = 60) or 80 mg qd (n = 55) and titrated to a maximum dose of 320 mg/day; doubling the dose every 2 weeks. Clinical and biochemical parameters were measured at Weeks 2, 4, 6, and 10. The average dose of valsartan at the end of study was 245 mg in the bid group vs 256 mg in the qd group (P = NS). Similar proportions of patients tolerated qd vs bid dosing (bid 67% vs qd 68%). Outcome measures including reduction in blood pressure, incidence of hypotension, renal impairment, orthostatic dizziness or fatigue, changes in serum K(+), creatinine, cystatin-C, and estimated glomerular filtration rate were similar between the 2 groups at all time-points. Brain natriuretic peptide levels decreased and plasma renin activity increased from baseline by the same amount in both groups at all time-points. Valsartan administered qd has a similar safety and tolerability profile with comparable 24-hour RAAS blockade, as assessed by increases in PRA, as bid dosing in patients with moderate to severe (NYHA class II-III) heart failure.

EFFECTS OF QUINAPRIL ADD-ON TREATMENT ON ALDOSTERONE BREAKTHROUGH IN PATIENTS WITH ESSENTIAL HYPERTENSION RECEIVING VALSARTAN: PP.24.466

Objective: Angiotensin II receptor antagonists (ARB) are the first choice for treatment on hypertension in patients with essential hypertension (EH). ARB decrease plasma aldosterone concentration (PAC). However, long-term ARB therapy is associated with increased PAC, which is known as ‘ealdosterone breakthrough’. Coadministration of ARB and angiotensin converting enzyme inhibitors (ACEI) is more effective for the treatment of hypertension than monotherapy of either. Nevertheless, little is known about the effect of coadministration of both agents on aldosterone breakthrough. Design and Method: The study was designed to compare the effects of adding quinapril (ACEI) to valsartan (ARB) and doubling the dose of valsartan in patients whose blood pressure did not reach the therapeutic goal (140/90 mmHg) by valsartan (80 mg/day) monotherapy. Sixty-six patients with EH (61±8 years old, 35 men and 31 women, serum creatinine levels <2 mg/dL) already on valsartan 80 mg/day were assigned to receive either a double dose of valsartan (160 mg) or quinapril (10 mg) added to valsartan (80 mg) for 48 weeks. Plasma renin activity (PRA) and PAC were measured at 0, 12, 24 and 48 weeks. Results: Both groups showed significant decreases in blood pressure during the treatment period. In the quinapril add-on group, PAC decreased from 94±6 at 0 week to 71±6 pg/mL at 12 weeks (P < 0.05) and maintained similar levels during therapy. However, in the valsartan double-dose group, PAC initially decreased from 92±8 (0 week) to 74±6 pg/mL (P < 0.05) at 12 weeks but returned to the baseline level (98±9 pg/mL) at 24 weeks. PRA increased from 2.1±0.4 (0 week) to 4.1±1.0 ng/mL/h (p < 0.05, 24 week) in the quinapril add-on group and from 2.6±0.6 (0 week) to 4.5±1.1 ng/mL/h (p < 0.05, 48 week) in the valsartan double-dose group. Conclusion: These findings suggest that adding quinapril to valsartan suppresses aldosterone breakthrough more effectively than increasing the dose of valsartan. Aldosterone increases cardiac fibrosis and promotes ventricular remodeling. Thus, coadministration of ACEI and ARB may minimize these aldosterone-induced deleterious effects.

Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, active comparator study

LCZ696 is a first-in-class inhibitor of the angiotensin II receptor and neprilysin. We aimed to establish whether the dual actions of LCZ696 lead to further lowering of blood pressure, compared with the angiotensin-receptor blocker valsartan. 1328 patients aged 18-75 years with mild-to-moderate hypertension were randomly assigned (double-blind) to 8 weeks' treatment in one of eight groups: 100 mg (n=156 patients), 200 mg (n=169), or 400 mg (n=172) LCZ696; 80 mg (n=163), 160 mg (n=166), or 320 mg (n=164) valsartan; 200 mg AHU377 (n=165); or placebo (n=173). The primary endpoint was the mean difference across the three single-dose pairwise comparisons of LCZ696 versus valsartan (100 mg vs 80 mg, 200 mg vs 160 mg, and 400 mg vs 320 mg) in mean sitting diastolic blood pressure during the 8-week treatment period. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00549770. 1215 patients completed the 8-week treatment period. The average reduction in mean sitting diastolic blood pressure across the doses of LCZ696 versus the appropriate comparator dose of valsartan showed significantly greater reductions with LCZ696 (mean reduction: -2.17 mm Hg, 95% CI -3.28 to -1.06; p<0.0001). The reduction in mean sitting diastolic blood pressure was significantly different for 200 mg LCZ696 versus 160 mg valsartan (-2.97 mm Hg, 95% CI -4.88 to -1.07, p=0.0023) and for 400 mg LCZ696 versus 320 mg valsartan (-2.70 mm Hg, -4.61 to -0.80, p=0.0055). LCZ696 was well tolerated and no cases of angio-oedema were reported; only three serious adverse events occurred during the 8-week treatment period, of which none was judged to be related to the study drug, and no patients died. Compared with valsartan, dual-acting LCZ696 provides complementary and fully additive reduction of blood pressure, which suggests that the drug holds promise for treatment of hypertension and cardiovascular disease. Novartis.

Antihypertensive effects of double the maximum dose of valsartan in African–American patients with type 2 diabetes mellitus and albuminuria

The blood pressure (BP)-lowering response to renin-angiotensin-aldosterone system blockade in hypertensive African-Americans is typically less than in whites. To determine whether higher than conventional doses of renin-angiotensin-aldosterone system blockade can improve BP reduction in African-American patients. Hypertensive patients with type 2 diabetes and albuminuria were enrolled: 110 African-Americans (BP = 150/87 mmHg, aged 57.5 +/- 11 years) and 281 non-African-Americans (BP = 151/89 mmHg, aged 57.7 +/- 11 years). All patients received valsartan 160 mg once daily in the morning for 4 weeks, following which patients were randomized to receive one of three valsartan doses: 160, 320 or 640 mg/day (2x, maximal recommended dose) for 26 weeks. If at week 6, target BP (<130/80 mmHg) was not achieved, then other add-on antihypertensives were allowed. The predominant BP (DeltaSBP/DeltaDBP) reduction was observed within 4 weeks and was lesser in African-Americans (7.8 +/- 15/4.5 +/- 9 mmHg) than non-African-Americans (8.9 +/- 14/6.6 +/- 1 mmHg, P < 0.05). Greater reduction in urinary albumin excretion was observed with higher doses (320 or 640 mg); however, the responses were similar between African-Americans and non-African-Americans. Use of add-on antihypertensives was higher in African-American (56%) vs. non-African-American patients (36%) with a similar rate across the three valsartan doses. From week 4-26, reduction in BP was lesser (P < 0.05) for African-American than non-African-American patients at the160-mg dose but not with 320 and 640-mg doses. In African-American patients, a lower BP reduction response was observed to conventional doses of valsartan than non-African-American patients, but at 640 mg, a higher response was observed in African-American patients than in non-African-American patients.

VALSARTAN IN EVERYDAY CLINICAL PRACTICE IN RUSSIA: ANTIHYPERTENSIVE EFFICACY AND INFLUENCE ON SEXUAL FUNCTION IN PATIENTS WITH ARTERIAL HYPERTENSION

Aim. To study antihypertensive efficacy and safety of valsartan-based therapy (Diovan, Novartis Pharma) as well as patient’s compliance and influence of treatment on several aspects of sexual function. Material and methods. 114 doctors from 81 medical institutions of Russia participated in this prospective multicenter observation study. 650 hypertensive patients (average age 53,9±0,4 y.o.) were enrolled. 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 questions 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 (37,5/18,5 and 37,6/15,9 mm Hg respectively, р<0,01 vs baseline). 312 patients (56,9% men, 43,1% women) completed sexual function survey. After 12 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 22 to 16% and from 44 to 30% respectively (р<0,05). Significant increase in the number of patients with 5-6 and 7-10 successful sexual attempts was observed (from 7 to 20% and from 0 to 7% respectively, р<0,05). The treatment resulted in significant increase in the number of patients, who characterized their sexual life satisfaction as “very satisfied” (from 11 to 25%, р<0,01). Conclusion. During the course of effective antihypertensive treatment there was a significant increase in 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.

FIXED COMBINATION OF VALSARTAN AND AMLODIPINE: EFFECTS ON THE LEFT VENTRICULAR HYPERTROPHY REGRESSION, ALBUMINURIA REDUCTION AND ENDOTHELIUM FUNCTION IN HYPERTENSIVE PATIENTS WITH METABOLIC SYNDROME

Aim. To study effects of fixed combination of valsartan and amlodipine on of left ventricular hypertrophy (LVH) regression, microalbuminuria reduction and endothelium function in hypertensive patients with metabolic syndrome (MS). Materials and methods. 20 hypertensive patients (15 females and 5 males) with metabolic syndrome and a history of previous ineffective antihypertensive therapy were studied. Combined antihypertensive therapy was applied during 12-24 weeks. Amlodipine and valsartan dose was 5/160 or 10/160 mg/day depending on blood pressure level. Endothelial function, blood pressure level, urinary albumin excretion and LVH regression were estimated. Results. Blood pressure reduction to the target level was revealed. There was a significant reduction in microalbuminuria by -55.3±39.2% (р=0.022) in comparison with the baseline. Endothelium-de???pendent vasodilation increased in 3.6±7.2% (р=0.05) in comparison with baseline, LVH decreased by -9.1±12.4 g/m2 (р=0.021). Conclusion. Therapy with fixed combination of valsartan and amlodipine results in blood pressure and microalbuminuria reduction, endothelium-dependent vasodilation improvement, LVH regression in hypertensive patients with MS. These findings show that the fixed combination of these antihypertensives has a multifaceted impact on cardiovascular risk.

Evaluation of Cardiac Function by Transthoracic Echocardiography in Subjects with ST-Segment Elevation Myocardial Infarction Following Primary Percutaneous Coronary Intervention according to Valsartan Dose: The Valsartan One Center Trial

The aim of this study was to evaluate the mid-term changes in cardiac function by transthoracic echocardiogram (TTE) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) according to valsartan dose. Between April 2006 and February 2009, 78 subjects (mean age: 57 ± 12 years, M : F = 74 : 4) with STEMI who underwent primary PCI were enrolled. Fifty three patients received low dose valsartan (40 or 80 mg) and 25 patients received high dose valsartan (160 or 320 mg). Follow-up TTE was done approximately 2 years later. We evaluated the changes in left ventricular (LV) function between initial and final TTE after primary PCI and compared the changes between low and high dose valsartan group. The mean follow-up TTE duration was 24 ± 8 months. Deceleration time (188.6 ± 56.3 msec vs. 221.5 ± 71.3 msec, p = 0.01), E/e' (12.24 ± 5.2 vs. 10.1 ± 4.9, p = 0.002), ejection fraction (52.7 ± 8% vs. 55.2 ± 8.4%, p < 0.01), and wall motion score index (1.45 ± 0.30 vs. 1.33 ± 0.32, p < 0.01) showed significant changes during the follow-up period. Wall motion improvement in injured myocardial segments was more frequently observed in the high-dose valsartan group compared to the low-dose group [18/25 (72%) vs. 24/53 (43.7%), p = 0.03]. There was no significant difference in the changes in cardiac dimensions and function between the low and high dose valsartan group. In patients with STEMI who undergoing primary PCI, high-dose valsartan treatment may be more helpful than low-dose in improving wall motion in the injured myocardium.

ANTIHYPERTENSIVE EFFICACY OF VALSARTAN IN SMOKERS VERSUS NON-SMOKERS WITH ARTERIAL HYPERTENSION: THE FIRST RESULTS OF RUSSIAN MULTICENTER OPEN STUDY

Aim. To study antihypertensive efficacy and safety of valsartan (Diovan, Novartis Pharma) as well as patient’s compliance to the mono- or combined valsartan based therapy in smoking vs non-smoking hypertensive patients. Material and methods. It was a prospective multicenter observation study. 114 doctors from 81 medical institutions of Russia participated in the study. 650 hypertensive patients (41,2% of smokers and 58,8% of non-smokers; age 53,9±0,4 y.o. in average) were included in the study. The evaluation of therapy efficacy was based on analysis of systolic (SBP) and diastolic (DBP) blood pressure (BP) changes and of patient number who answered to the treatment and reached BP target level. Safety and compliance of the treatment also was analyzed. The initial valsartan dose was 80 mg OD and may be increased (up to 320 mg OD) by doctor for achievement of BP target level. A combination of the valsartan with hydrochlorothiazide was also allowed. Amlodipine (5-10 mg/d) or any other antihypertensive also may be added if necessary. Results. Significant decrease of SBP and DBP was observed in each group between the 1st and 5th visits. SBP decreased by 37,5 mm Hg (р&lt;0,01) in smoking patients and by 37,6 mm Hg (р&lt;0,01) in non-smoking ones. DBP decreased by 18,5 mm Hg (р&lt;0,01) in smoking patients and by 15,9 mm Hg (р&lt;0,01) in non-smoking ones. Differences in SBP and DBP changes were not significant between groups. Target BP level (&lt;140/90 mm Hg) was reached in 96,2% of smokers and in 96% of non-smokers. 99% of smoking patients and 96,1% of non-smoking ones responded to valsartan based therapy according to defined criteria. Conclusion. Similar antihypertensive efficacy and safety of valsartan mono- and combined therapy was found out in smoking and non-smoking hypertensive patients.

Rationale for the use of sartans in patients with arterial hypertension

Angiotensin II (ATII) receptor antagonists, the drugs that affect the basic links of neuro-humoral regulation: the renin-angiotensin-aldosterone (RAAS) and sympathicoadrenal systems, have currently found wide use in clinical cardiology. By blocking the specific ATII receptors, the agents of this group contributes to systemic vasodilation, cell growth inhibition, including to the suppressed proliferation of endothelial and smooth muscle cells of the vascular wall, fibro-blasts, and to the inhibited cardiomyocytic hypertrophy. ATII receptor antagonists are referred to as first-line drugs used in the treatment of arterial hypertension (AH) in young patients in whom RAAS activity is generally increased, in that of diabetes mellitus since the drugs of this group are able to reduce the degree of microalbuminuria/proteinuria, and in the complex therapy for chronic heart failure (CHF). One of the representatives of this group is valsartan, a non-heterocyclic derivative, has a double elimination pathway (the liver and kidneys), a sustained 24-hour antihypertensive effect after single administration, which allows its once-daily dosing, by correcting systolic and diastolic blood pressure in more than 70% of patients. It should be emphasized that adjustment of the dose of valsartan is not required in moderately diminished hepatic or renal function. Valsartan failed to exert a negative effect on the level of glycemia and to cause changes in lipid profile and triglyceride levels. The long-term use of valsartan as mono-therapy for AH requires that the safety of treatment should not undergo additional laboratory monitoring. A multicenter, double-blind, placebo-controlled Val-HeFT trial covering 5010 pa-tients with CHF and a left ventricular ejection fraction (EF) of less than 40%, demonstrated that valsartan produced good clinical effects. Although overall mortality (one of the primary end points) was similar in the valsartan and placebo groups; another end point (reductions in the risk of mortality and morbidity) and the frequency of hospitalizations for increased symptoms of CHF was decreased in the valsartan group by 13.2 and 27.5%; respectively. In addition, valsar-tan was found to have a positive effect on a number of secondary end points: quality of life sig-nificantly improved, EF of the left ventricle rose, its dimensions decreased, and the degree of CHF symptoms was reduced, exercise tolerance increased, and the plasma levels of norepineph-rine, atrial natriuretic peptide, and aldosterone were decreased. The adverse reactions caused by ATII antagonists are seen rather rarely, which provides high patient compliance to some extent. The contraindications to the use of ATII antagonists are their hypersensitivity, arterial hypotension, hyperkalemia, dehydration, bilateral renal artery stenosis, pregnancy, childhood.

Effectiveness of initiating treatment with valsartan/hydrochlorothiazide in patients with stage-1 or stage-2 hypertension

This prospective, 6-week, multicenter, double-blind study examined the benefits of initiating treatment with combination valsartan/hydrochlorothiazide (HCTZ) compared with initial valsartan monotherapy for 648 patients with stage-1 or stage-2 hypertension (age=52.6±10 years; 54% male; baseline blood pressure (BP)=161/98 mm Hg, 32% stage 1). Patients were randomized to valsartan 80 mg (V-low), valsartan 160 mg (V-high) or valsartan/HCTZ 160/12.5 mg (V/HCTZ), and electively titrated after weeks 2 and 4 to the next dosage level (maximum dose valsartan/HCTZ 160/25 mg) if BP remained >140/90 mm Hg. At end of the study, patients initiated with V/HCTZ required less titration steps compared with the initial valsartan monotherapy groups (63 vs 86% required titration by study end, respectively) and reached the target BP goal of <140/90 mm Hg in a shorter period of time (2.8 weeks) (P<0.0001) vs V-low (4.3 weeks) and V-high (3.9 weeks). Initial combination therapy was also associated with higher BP control rates and greater reductions in both systolic and diastolic BP from baseline (63%, −27.7±13/–15.1±8 mm Hg) compared with V-low (46%, −21.2±13/−11.4±8 mm Hg, P<0.0001) or V-high (51%, −24.0±13/−12.0±10 mm Hg, P<0.01). Overall and drug-related AEs were mild to moderate and were similar between V/HCTZ (53.1 and 14.1%, respectively) and the two monotherapy groups, V-low (50.5 and 13.8%) and V-high (50.7 and 11.8%). In conclusion, initiating therapy with a combination of valsartan and low-dose HCTZ results in early, improved BP efficacy with similar tolerability as compared with starting treatment with a low or higher dose of valsartan for patients with stage-1 and stage-2 hypertension.

Randomized study to compare valsartan &amp;plusmn; HCTZ versus amlodipine &amp;plusmn; HCTZ strategies to maximize blood pressure control

Delays in achieving blood pressure (BP) control may increase morbidity and mortality in patients with hypertension. Thus, deciding which antihypertensive agent to use and at what dosage, in addition to determining when to initiate combination therapy and which agents to combine, is important for achieving BP control. This randomized, double-blind, 14-week study was conducted to compare the efficacy and tolerability of various doses of valsartan +/- hydrochlorothiazide (HCTZ) versus amlodipine +/- HCTZ for maximizing BP control in 1,285 patients with uncontrolled hypertension. Patients with stage 1 hypertension and naïve to antihypertensive therapy (33.9%) started valsartan 160 mg or amlodipine 5 mg. Treatment-naïve patients with stage 2 hypertension (13.5%) or those uncontrolled on current antihypertensive monotherapy (52.6%) started valsartan 160 mg/HCTZ 12.5 mg or amlodipine 10 mg. At weeks 4, 8, and 11, patients not achieving BP control were up-titrated (maximum: valsartan 320 mg/HCTZ 25 mg, amlodipine 10 mg/HCTZ 25 mg). At study end, 78.8% of patients on valsartan +/- HCTZ were controlled (BP <140/90 mmHg) and still on study medication versus 67.8% on amlodipine +/- HCTZ (P < 0.0001). Amlodipine-treated patients had a higher incidence of peripheral edema (22.4% vs 2.2%) and associated discontinuations (7.3% vs <1%). Initiating therapy earlier with valsartan/HCTZ, rather than titrating monotherapy to its maximum dose before adding a second agent, was superior to amlodipine monotherapy or amlodipine +/- HCTZ for achieving BP control, and avoided excessive treatment adjustments and maintained tolerability.

A randomized, double‐blind, placebo‐controlled study to determine the effects of valsartan on exercise time in patients with symptomatic heart failure with preserved ejection fraction

AimsTo determine whether valsartan improves treadmill exercise time, in patients with symptomatic heart failure with a preserved ejection fraction (HFPEF), compared with placebo.Methods and resultsIn this multicentred, double-blind, 14-week study, patients were randomized to receive valsartan (V) 80 mg or placebo (P) once daily on top of background medications. The dose of valsartan was force-titrated up to 320 mg. A total of 152 patients were randomized (V = 70, P = 82). Most patients had well-controlled hypertension (V = 91.2%, P = 89.0%) (mean baseline systolic BP ∼130 mmHg) and >50% were receiving an angiotensin-converting enzyme inhibitor and/or beta-blocker (V = 57.4%, P = 54.9%). The mean ejection fraction at baseline was 70.48% in the placebo group (n = 64) and 71.52% in the valsartan group (n = 79). Valsartan had no significant effect on exercise time (primary variable), gas exchange variables, 6 min walk test distance, exertion-related symptoms, brain natriuretic peptide levels, echocardiographic parameters, or quality-of-life scores. Valsartan significantly lowered peak exercise systolic BP (−13.1 mmHg vs. placebo; P < 0.001) and improved ratings of perceived exertion (Borg score) (−0.69 vs. placebo; P = 0.008).ConclusionIn this population, which predominantly included patients with well-controlled hypertension and symptomatic HFPEF, addition of valsartan did not increase exercise time within 14 weeks. However, valsartan 320 mg reduced blood pressure and improved symptoms of perceived exertion (Borg score) during exercise and was generally well-tolerated.