Effectiveness and safety of valsartan in children aged 6 to 16 years with hypertension

Abstract

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.

Figure 1

Study design: a placebo‐controlled washout preceded a 2‐week, randomized, dose‐ranging phase (phase 1), followed by a 2‐week, randomized, placebo‐controlled, withdrawal phase (phase 2). Patients were then permitted to roll over into a 52‐week, open‐label extension phase to assess long‐term valsartan safety. Valsartan dosing began at 40 mg/d and could be increased every 2 weeks incrementally to 160 mg/d. Hydrochlorothiazide 12.5 mg daily could be added if the blood pressure (BP) remained ≥95th percentile with the highest dose of valsartan (160 mg/d).

Figure 2

Mean changes in trough sitting systolic blood pressure (SSBP) and sitting diastolic blood pressure (SDBP) in children (aged 6–16 years) randomized to receive 1 of 3 dose levels of valsartan (phase 1) for 2 weeks (low dose=10/20 mg; medium dose=40/80 mg; high dose=80/160 mg). The size of the circles is proportional to the number of patients in each group.

Figure 3

(A) Plot of the slope analysis for the change in mean sitting systolic blood pressure (SSBP) from baseline to the end of phase 1 according to subgroup (intent‐to‐treat population). Estimates of the slope with 95% confidential intervals (CIs) are shown. (B) Plot of between‐group difference in the mean change in SSBP (mm Hg) from the end of phase 1 to the end of phase 2 for patients treated with valsartan. Data are presented according to subgroup. Estimates of the mean change difference with 95% CI are shown. The size of the circles is proportional to the number of patients in each group.

Figure 4

Changes in sitting systolic blood pressure (SSBP) and sitting diastolic blood pressure (SDBP) from the end of phase 1 to the end of phase 2.