Candesartan cilexetil in children and adolescents aged 1 to <17 years with hypertension: profile report.
In pediatric patients, normal blood pressure (BP) is a function of age, sex, and height percentile; thus, diagnosing hypertension in children and adolescents requires reference to a population distribution. According to the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents and the European Society of Hypertension guidelines, hypertension in pediatric patients is defined as systolic BP (SBP) and/or diastolic BP (DBP) persistently exceeding the 95th percentile. It may manifest secondary to another disease process, such as coarctation of the aorta, endocrine disease, or renal disease, with the likelihood of there being an underlying disease inversely related to age anddirectly related to the degree ofBP elevation.Hypertension may also manifest without identifiable cause (essential hypertension). Although, as in adults, essential hypertension is more prevalent than secondary hypertension in pediatric patients, it is rarely observed in infants and young children; the prevalence of essential hypertension is significantly elevated in adolescence and often associated with excess weight and a family history of hypertension or cardiovascular disease. Although the long-term sequelae associatedwith hypertension (e.g. heart failure, kidney disease, myocardial infarction, and stroke) rarely manifest in children, elevated BP levels are predictive of the development of adult hypertension and are associated with the early markers of cardiovascular disease, including atherosclerosis, decreased arterial compliance, diastolic dysfunction, increased intima-media thickness, and left ventricular hypertrophy. Thus, correctly identifying and evaluating pediatric patients with elevated BP levels may improve the accuracy of predicting hypertension in later life and avert the cardiovascular consequences of hypertension. Candesartan cilexetil (Atacand ) is the orally administered prodrug of candesartan, an angiotensin II subtype 1 receptor antagonist. The features and properties of candesartan cilexetil are presented in table I. The pharmacokinetics (area under the plasma concentrationtime curve andmaximumplasma concentration) of candesartan do not appear to be affected by age, sex, or weight, with a similar exposure observed in children aged 1 to <6 years or >6 years and adults. Therapy with candesartan cilexetil 0.05, 0.20, and 0.40mg/ kg/day for 4 weeks was effective in the treatment of hypertension in children aged 1 to <6 years, inducing significant dosedependent reductions from baseline in sitting SBP (SSBP) [primary endpoint] and sitting DBP (SDBP) in the doubleblind phase of a randomized, parallel-group, multinational, dose-ranging clinical study. The criteria for antihypertensive response (SBP and DBP values that were less than the 95th percentile) were met by 28–66% of patients. The beneficial antihypertensive effects of candesartan cilexetil therapy were sustained for up to 160 weeks. No significant difference from zero in the slope of the placebo-adjusted change in SSBP (primary endpoint) and SDBP was observed across the three candesartan cilexetil treatment groups (candesartan cilexetil 2, 8, or 16mg/day in patients weighing <50 kg and candesartan cilexetil 4, 16, or 32mg/day in patients weighing ‡50 kg) during the double-blind phase of a randomized, double-blind, parallel-group, placebo-controlled, multinational, dose-ranging study in children and adolescents aged 6 to <17 years. Nonetheless, candesartan cilexetil demonstrated significantly greater changes from baseline to the end of the double-blind phase than placebo in SSBP and SDBP,