Long-term safety and tolerability of valsartan in children aged 6 to 17 years with hypertension

Abstract

Objective: The present study aimed to assess the long-term safety and tolerability of valsartan in hypertensive children aged 6-17 years, with or without chronic kidney disease (CKD).

Methods: This was an 18-month, open-label, multicentre, prospective study conducted in 150 patients with history of hypertension with or without CKD. The primary endpoint was long-term safety and tolerability of valsartan and valsartan-based treatments, assessed in terms of adverse events (AEs), serious AEs, laboratory measurements, estimated glomerular filtration rate (eGFR), urinalysis and electrocardiogram.

Results: Of 150 enrolled patients, 117 (78%) completed the study. At week 78, a clinically and statistically significant reduction in mean sitting systolic and diastolic blood pressures was observed in all patients (- 14.9 mmHg and - 10.6 mmHg, respectively). Within the first 3 months of treatment, mean urine albumin creatinine ratio decreased in CKD population, which was sustained. A higher percentage of CKD patients had at least one AE compared to non-CKD patients (85.3% vs. 73.3%, respectively). The majority of AEs were mild (50.7%) or moderate (18.7%) in severity. As expected, in patients with underlying CKD, increases in serum potassium, creatinine and blood urea nitrogen were more commonly reported compared to non-CKD patients. A > 25% decrease in Schwartz eGFR was observed in 28.4% of CKD patients and 13.5% of non-CKD patients.

Conclusions: Valsartan was generally well tolerated, with an AE profile consistent with angiotensin receptor blockers in the overall population and in patients with underlying CKD. Long-term efficacy was maintained and a beneficial effect on proteinuria was observed.

Keywords: Chronic kidney disease; Hypertension; Long-term safety; Paediatric; Valsartan.

Fig. 1

Study design. The starting and maintenance doses of valsartan were assigned according to three weight categories: ≥ 18 to < 35 kg, 40 mg and 80 mg; ≥ 35 to < 80 kg, 80 mg and 160 mg; and ≥ 80 to ≤ 160 kg, 160 mg and 320 mg, respectively. Amlo amlodipine, HCTZ hydrochlorothiazide, RAAS renin-angiotensin aldosterone system, Val valsartan

Fig. 2

msSBP and msDBP in patients by visit (full analysis set). Number of patients at a given visit was the number of patients with both baseline and visit values at that visit. *p < 0.0001, baseline vs. post-baseline visit. Antihyp antihypertensives, msDBP mean sitting diastolic blood pressure, msSBP mean sitting systolic blood pressure

Fig. 3

Change from baseline BP achieved in patients at the endpoint of treatment. The endpoint is week 78 or the last post-baseline observation carried forward value. *p values were based on an ANCOVA model with CKD strata as factors and centred-baseline MSBP/MSDP as the covariate. There was significant baseline imbalance (p < 0.05) in msDBP but not msSBP at baseline between CKD and non-CKD groups and a significant baseline-by-CKD-group interaction (p < 0.05) in assessment of difference between CKD and non-CKD groups in msDBP reduction from baseline. BP blood pressure, CKD chronic kidney disease, LS least square, msDBP mean sitting diastolic blood pressure, msSBP mean sitting systolic blood pressure

Fig. 4

Mean UACR in CKD patients by visit. Number of patients at a given visit was the number of patients with both baseline and visit values at that visit. *p < 0.05. Antihyp antihypertensives, UACR urine albumin creatinine ratio, VAL valsartan