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 simvastatin 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.
Simvastatin Pravastatin Lovastatin DHEAS Probucol
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This study was financially supported by Merck & Co., Inc., USA. The authors would like to thank the study site coordinators and investigators as well as the Merck subsidiary personnel. Special thanks are given to Laura Corsetti for project coordination. Dr Kastelein is an established investigator of the Netherlands Heart Foundation (grant no. 2000D039).
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