Efficacy and Safety of the Angiotensin Receptor Blocker Valsartan in Children With Hypertension Aged 1 to 5 Years

Abstract

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...

A Randomized, Open-Label, Dose-Response Study of Losartan in Hypertensive Children

“…Similar results were reported in a study of the ARB valsartan in 90 children aged 1-6 years (4). The authors of this study suggested that young children may be uniquely sensitive to treatment, and a lower starting dose might have facilitated demonstration of a dose response (4). Renin levels are higher in younger children, possibly contributing to greater sensitivity to renin-angiotensin-aldosterone system blockade (11); however, this association could not be tested because renin was not measured in the present study.…”

Clinical and Demographic Characteristics of Children With Hypertension

“…Study A2307 6 was performed at 36 centers in 7 countries, and Study A2302 7 was performed at 55 centers in 9 countries. Institutional review boards/ethics committees at each participating center reviewed and approved the study protocols; written informed consent/assent was obtained for all of the study participants according to local requirements.…”

“…6,7 In this report we have pooled the baseline clinical and demographic data on the subjects enrolled in those trials to better describe the characteristics of such patients in the current era.…”

2016 European Society of Hypertension guidelines for the management of high blood pressure in children and adolescents

“…They have a powerful, dosedependent antiproteinuric action in pediatric nephropathies (231). RAS inhibitors in general have a favourable side effect profile; however, a few fatalities have been documented in infants with acute intravascular volume depletion while receiving angiotensin receptor blockers (231,232). It is recommended to use RAS blocking agents as first choice with 40 appropriate risk counselling in all proteinuric patients with CKD.…”