Abstract-The efficacy and safety of valsartan were studied in 90 children (mean age: 3.2 years; 60% male; 30% black) with systolic blood pressure (SBP) Ն95th percentile. Nineteen percent received valsartan in addition to previous antihypertensive therapy. Subjects were randomly assigned to low-, medium-, or high-dose valsartan for 2 weeks (phase 1) and then reassigned randomly to placebo or to remain on the same valsartan dose for 2 additional weeks (phase 2). After this, subjects were enrolled into a 52-week, open-label phase during which valsartan was dosed to achieve SBP Ͻ95th percentile. Statistically significant reductions in SBP and diastolic blood pressure of Ϸ8.5 mm Hg and 5.7 mm Hg, respectively, were observed at the end of phase 1 in all of the valsartan dose groups. SBP and diastolic blood pressure were also significantly lower during phase 2 in valsartan recipients compared with placebo recipients. SBP Ͻ95th percentile was achieved in 77.3% of subjects during the open-label phase. Adverse events were minor and occurred at similar frequencies in each of the 3 dose groups in phase 1 and at equal frequencies in the valsartan and placebo arms in phase 2. Serious adverse events and drug-related adverse events occurred infrequently during both the double-blind (2.2% and 5.6%, respectively) and open-label (14.8% and 6.8%, respectively) portions of the study.Valsartan treatment had no demonstrable negative effects on growth and development. In this study, the first trial of an antihypertensive agent conducted in children To date, however, all of these studies have been conducted in children Ͼ6 years old, leaving a significant information deficit regarding the treatment of hypertension in younger children, most of whom have underlying kidney disease or other secondary causes of hypertension. [3][4][5] Valsartan is an angiotensin II receptor blocker approved in adults for the treatment of hypertension, heart failure, and left ventricular failure or left ventricular dysfunction postmyocardial infarction. 6 Its effects primarily result from selective blockade of the angiotensin type I receptor in vascular smooth muscle and adrenal gland. 6,7 Valsartan effectively reduces systolic blood pressure (BP; SBP) and diastolic BP (DBP) in adults, both as monotherapy and in combination with other antihypertensive agents, displaying similar antihypertensive efficacy to other antihypertensive drug classes. [7][8][9][10] Given its effects on angiotensin blockade, valsartan may also reduce proteinuria and have other beneficial effects in patients with underlying kidney disease. 10 For these reasons, valsartan is an attractive drug for use in young children with hypertension.This study was conducted to explore the efficacy of valsartan in reducing BP in children aged 1 to 5 years with hypertension. We also examined the safety and tolerability of both short-and long-term administration of valsartan in this population. MethodsThis was a double-blind, randomized, multicenter study sponsored by Novartis Pharmaceuticals and perfor...

Abstract-Most information describing hypertension in the young comes from single-center reports. To better understand contemporary demographic and clinical characteristics of hypertensive children and adolescents, we examined baseline data on 351 children aged 1 to <17 years old who were enrolled in 2 multicenter trials of valsartan. Anthropometric, laboratory, and demographic information at randomization was extracted from the clinical trials databases. Summary variables were created and compared for 3 age groups: <6 years (n=90), 6 to <12 years (n=131), and 12 to <17 years (n=130). Comparisons were also made between different etiologies of hypertension and for different anthropometric categories. Children <6 years old were significantly more likely to have secondary hypertension and were significantly less likely to have weight or body mass index >95 percentile compared with older children. Estimated glomerular filtration rate was significantly lower in children <6 years old (90.9±31.8 mL/min per 1.73 m 2 ) than in the other 2 age groups (6 to <12 years, 141.4±42.1 mL/min per 1.73 m 2 ; 12 to <17 years, 138.3±46.0 mL/min per 1.73 m 2 ). Frequency of total cholesterol >95 percentile was significantly lower in children aged <6 years. Diastolic blood pressure index (subject blood pressure÷95 percentile) was significantly higher in children <6 years old (1.1 versus 1.0 in both the 6 to <12 years and 12 to <17 years groups; both P<0.0001). We conclude that hypertensive children <6 years are more likely to have secondary hypertension and to have higher diastolic blood pressure and lower glomerular filtration rate and are less likely to be obese or to have elevated cholesterol than school-aged children or adolescents. These findings emphasize unique aspects of childhood hypertension that should be considered when evaluating children and adolescents with elevated blood pressure and in designing future clinical trials.

The effectiveness and safety of valsartan have not been assessed in hypertensive children. Therefore, hypertensive patients aged 6 to 16 years (n=261) were randomized to receive weight‐stratified low‐ (10/20 mg), medium‐ (40/80 mg), or high‐dose (80/160 mg) valsartan for 2 weeks. After 2 weeks, patients were randomized to a 2‐week placebo‐controlled withdrawal phase. Dose‐dependent reductions in sitting systolic blood pressure (SSBP) and sitting diastolic blood pressure (SDBP) were observed after 2 weeks (low dose, −7.9/−4.6 mm Hg; medium dose, −9.6/−5.8 mm Hg; high dose, −11.5/−7.4 mm Hg [P<.0001 for all groups]). During the withdrawal phase, SSBP and SDBP were both lower in the pooled valsartan group than in the pooled placebo group (SSBP, −2.7 mm Hg [P=.0368]; SDBP, −3.0 mm Hg [P=.0047]). Similar efficacy was observed in all subgroups. Valsartan was well tolerated and headache was the most commonly observed adverse event during both the double‐blind and 52‐week open‐label phases. J Clin Hypertens (Greenwich). 2011;13:357–365. ©2011 Wiley Periodicals, Inc.

While the epidemiology of adult heart failure has been extensively researched, this systematic review addresses the less well characterized incidence and prevalence of pediatric HF. The search strategy used Cochrane methodology and identified 83 unique studies for inclusion. Studies were categorized according to whether the HF diagnosis was reported as primary (n = 10); associated with other cardiovascular diseases (CVDs) (n = 49); or associated with non-CVDs (n = 24). A narrative synthesis of the evidence is presented. For primary HF, the incidence ranged from 0.87/100,000 (UK and Ireland) to 7.4/100,000 (Taiwan). A prevalence of 83.3/100,000 was reported in one large population-based study from Spain. HF etiology varied across regions with lower respiratory tract infections and severe anemia predominating in lower income countries, and cardiomyopathies and congenital heart disease major causes in higher income countries. Key findings for the other categories included a prevalence of HF associated with cardiomyopathies ranging from 36.1% (Japan) to 79% (US); associated with congenital heart disease from 8% (Norway) to 82.2% (Nigeria); associated with rheumatic heart diseases from 1.5% (Turkey) to 74% (Zimbabwe); associated with renal disorders from 3.8% (India) to 24.1% (Nigeria); and associated with HIV from 1% (US) to 29.3% (Brazil). To our knowledge, this is the first systematic review of the topic and strengthens current knowledge of pediatric HF epidemiology. Although a large body of research was identified, heterogeneity in study design and diagnostic criteria limited the ability to compare regional data. Standardized definitions of pediatric HF are required to facilitate cross-regional comparisons of epidemiological data.Electronic supplementary materialThe online version of this article (10.1007/s00246-017-1787-2) contains supplementary material, which is available to authorized users.