Untreated pediatric hypertension can have “devastating effects,” including left ventricular hypertrophy and chronic kidney disease, the researchers note in a report published online April 12th in Hypertension. The goal of treatment is to reduce blood pressure below the 95th percentile for age, gender, and height (below the 90th percentile for patients with diabetes, glomerular kidney disease, or a family history of hypertension).
In response to a request from the U.S. Food and Drug Administration, Dr. Reinilde Heyrman from Daiichi Sankyo Pharma Development in Parsippany, New Jersey, and the AESOP Study Group evaluated the efficacy, safety and dose-response relationship of olmesartan in children between the ages of 6 and 16 with hypertension (on average, approximately 12 years old).
“Not all blood pressure can be controlled through lifestyle changes, requiring medication, even among children,” said Jennifer Brennan, from Daiichi Sankyo, in email to Reuters Health. Brennan was not involved in the study.
The investigators studied two cohorts. Cohort A comprised patients of various races (18% black, 62% white, 10% Asian, 14% “other,” n = 190), and cohort B consisted only of black children (n = 112).
The randomized trial involved two phases, a 3-week, dose-ranging active treatment period and a subsequent 2-week, placebo-controlled, withdrawal period.
In the treatment period, children weighing 20 to 34 kg received either 2.5 mg or 20 mg of olmesartan daily, and children weighing 35 kg or more received either 5 mg or 40 mg. During the withdrawal phase, the authors randomly assigned subjects to either continue on their same dose or switch to placebo.
From baseline to the end of the 3-week treatment phase, seated trough systolic and diastolic blood pressures in cohort A fell by 7.8 and 5.5 mmHg, respectively, with low-dose olmesartan and by 12.6 and 9.5 mmHg, respectively, with the high doses.
In cohort B, systolic and diastolic blood pressures fell by 4.7 and 3.5 mmHg, respectively, with low-dose treatment and by 10.7 and 7.6 mmHg, respectively, with high-dose olmesartan.
Reductions were consistently greater with the high doses, and in cohort A vs cohort B. According to the researchers, the latter finding is likely due to reduced responsiveness to renin-angiotensin-aldosterone system-blocking agents, as has previously been observed in adult black populations.
Linear regression analyses showed significant dose responses in both cohorts and in the combined population, before and after adjusting for body weight.
One hundred eighty-one patients in cohort A and 105 in cohort B completed the withdrawal phase of the trial. During this 2-week period, blood pressure control was maintained in patients who continued olmesartan but decreased in patients who switched to placebo. The difference between placebo and olmesartan was not statistically significant in cohort B, which the authors attribute to the small sample size.
Olmesartan was well tolerated at all doses, the authors report. The most common treatment-emergent adverse events were headache and dizziness – but the researchers caution that more side effects may emerge during longer term treatment.
“The approval of Benicar for the treatment of high blood pressure in pediatric patients gives doctors a safe and effective tool to help many of the estimated 3.6 million American children and adolescents with high blood pressure, the majority of whom are unaware they have the condition,” Brennan concluded.
The study was supported by Daiichi Sankyo, Inc.