Efficacy, safety and tolerability of simvastatin in children with familial hypercholesterolaemia - Rationale, design and baseline characteristics

Objective: To describe the rationale, design and baseline data of a study conducted to determine the efficacy, safety and tolerability of simvastatin in children and adolescents with heterozygous familial hypercholesterolaemia (heFH). Methods: Patients were recruited from nine lipid clinics worldwide. After a 4-week diet/placebo run-in period, patients were randomised to receive either simvastatin or placebo, Simvastatin was started at 10 mg/day and titrated at 8-week intervals to 20 and then 40 mg/day. During a second 24-week extension period, patients continued to receive sirrivastatin 40mg or placebo daily according to the original allocation. Results: A total of 173 patients [98 boys (average age 13.2 years), 75 girls (average age 14.5 years)] were included in the study. Baseline total cholesterol (total-C) and low-density lipoprotein cholesterol (LDL-C) were severely elevated in heFH boys and girls compared with 69 healthy non-affected controls who were not part of the study. In heFH boys and the male siblings, respectively, mean total-C was 6.78 +/- 1.03 vs 3.80 +/- 0.11 mmol/L (p < 0.001), and mean LDL-C was 5.09 +/- 0.97 vs 2.53 +/- 0.69 mmol/L (p < 0.001). In heFH girls and the female siblings, respectively, mean total-C was 7.44 +/- 1.35 vs 4.24 +/- 0.47 mmol/L (p < 0.001), and mean LDL-C was 5.68 +/- 1.28 vs 2.44 +/- 0.50 mmol/L (p < 0.001). Conclusion: This is the first and largest randomised, controlled, long-term clinical study to test the efficacy, safety and tolerability of a statin in boys and girls with heFH. The baseline data suggest that the sample selected for this study is representative of patients with heFH.