High-dose valsartan reduces systolic BP in children with hypertension

Treatment with a higher rather than a lower dose of valsartan led to significantly greater reductions in systolic blood pressure (BP) in children with hypertension, regardless of their chronic kidney disease (CKD) status, according to a study presented at ESC 2019.

This study involved 127 children (mean age 3.26 years, 63.0 percent boys) with hypertension (defined as mean systolic BP of ≥95^th percentile) who were randomized to receive valsartan at either 0.25 or 4 mg/kg per day for a 6-week double-blind period (phase I), followed by valsartan 1 mg/kg per day with an optional titration of 2–4 mg/kg per day for a 20-week open-label period (phase II). The primary endpoint was to evaluate the dose-dependent reduction in mean systolic BP from baseline to 6 weeks. [ESC 2019, abstract P4555]

A total of 120 patients completed phase I, while 114 patients completed phase II, of whom 55 had CKD (mean age, 2.86 years) and 59 did not (mean age, 3.66 years).

At 6 weeks, those who received valsartan 4 mg/kg had a significantly greater reduction in mean systolic BP from baseline than those on 0.25 mg/kg (8.5 vs 4.1 mm Hg; p=0.0157).

This significantly greater reduction in systolic BP applied to patients with CKD who received valsartan 4 mg/kg compared with 0.25 mg/kg (9.2 vs 1.2 mm Hg; p=0.0096).

A greater, but not significant, reduction in mean systolic BP at 6 weeks was also observed among patients without CKD who received valsartan 4 vs 0.25 mg/kg (7.8 vs 6.9 mm Hg; p=0.6531).

A clinically and statistically significant decrease in mean diastolic BP was also observed among patients treated with 4 vs 0.25 mg/kg valsartan (6.8 vs 0.3 mm Hg; p<0.0001), among those with CKD (6.5 vs 4.0 mm Hg; p=0.0030) and without CKD (7.2 vs 1.9 mm Hg; p=0.0042).

Overall, both mean systolic and diastolic BP decreased were sustained at 6–26 weeks in all patients, irrespective of their CKD status.

Adverse events (AEs) occurred at a lower rate in the valsartan 4 vs 0.25 mg/kg arm (41.9 percent vs 51.6 percent). Serious AEs occurred in 3.2 percent of patients at a comparable rate between the two treatment groups.

Respiratory tract infection (5.6 percent), cough or diarrhoea (4.8 percent), and bronchitis (4.0 percent) were the most common AEs reported in both treatment arms.

“[High-dose] valsartan produced clinically relevant reductions in BP with a statistically significant dose-response in children aged 1–5 years with hypertension, with or without CKD. Long-term efficacy was maintained and was generally well-tolerated,” the researchers concluded.