Objective-Functional and morphological changes of the arterial wall already present in young children with heterozygous familial hypercholesterolemia (HeFH) suggest that treatment should be initiated early in life to prevent premature atherosclerotic cardiovascular disease. The purpose of this study was to assess the efficacy and particularly safety of statin therapy in children with HeFH. Methods and Results-We performed a meta-analysis of randomized, double-blind, placebo-controlled trials evaluating statin therapy in children aged 8 to 18 years with HeFH. Six studies (nϭ798 children) with 12 to 104 weeks of treatment were included. Total cholesterol, LDL cholesterol, and apolipoprotein B were significantly reduced, whereas HDL cholesterol and apolipoprotein A1 were significantly increased by statin therapy. No statistically significant differences were found between statin-and placebo-treated children with respect to the occurrence of adverse events (RR 0.

Familial hypercholesterolemia (FH) is a prevalent (1:500 individuals) inherited disorder that strongly predisposes to premature atherosclerosis and subsequent cardiovascular disease. 1 In children with FH, atherosclerosis progression is observed before puberty. 2 Consequently, guidelines for FH treatment advocate initiation of statins in children as young as 8 years. 3 However, longterm efficacy and safety data for statin therapy initiated during childhood do not exist. We followed up a cohort of children with FH receiving statin therapy until adulthood.Methods | We conducted a cohort study of 214 children heterozygous for FH, living in the Netherlands, aged 8 to 18 years, who were randomized between 1997 and 1999 into a singlecenter, 2-year, double-blind, placebo-controlled trial of pravastatin. 4 Results showed a significant regression of carotid intima-media thickness (IMT) after statin treatment compared with placebo.After the trial, all children received pravastatin (20-40 mg/d) and were followed up until March 2011 along with 95 unaffected siblings. Patients were instructed to adhere to the Step 2 diet. During follow-up, several patients switched to other statins. After 10 years, all participants underwent a physical examination, fasted blood sample, assessment of family and medical history, including the occurrence of adverse events,The low-density lipoprotein levels of patients with FH at follow-up did not meet current treatment standards and carotid IMT was thicker than in unaffected siblings. More robust lipid-lowering therapy or earlier initiation of statins may be required to completely restore arterial wall morphology and avert cardiovascular events later in life in this high-risk population.

In children with familial hypercholesterolemia, rosuvastatin 20 mg daily reduced LDL-C by 50%. Nonetheless, only 40% attained the consensus LDL-C target of <110 mg/dl, reflecting these patients' high baseline LDL-C levels (mean, 232 mg/dl). (Pediatric Lipid-Reduction Trial of Rosuvastatin [PLUTO]; NCT00355615).

Coadministration of ezetimibe with simvastatin was safe, well tolerated, and provided higher LDL-C reduction compared with simvastatin alone in adolescents with HeFH studied up to 53 weeks. (Effects of Ezetimibe With Simvastatin in the Therapy of Adolescents With Heterozygous Familial Hypercholesterolemia; NCT00129402).