de Jongh 2002a

Methods	* Design: RCT * Randomization process: nr * Blinding: double * Concealment of allocation: nr * Setting: 7 countries, 9 medical centers * Country: Canada, Costa Rica, France, Netherlands, New Zealand, Norway * Follow‐up: 24 and 48 weeks
Participants	Individuals with HeFH (N = 175) * Diagnosis: 1 parent clinical FH, LDL‐C > 4.1mmol/L * Inclusion: age ≦ 18 years; HeFH; LDL‐C > 95th percentile; genetic diagnosis or family history of high LDL‐C * Exclusion: smoking; vasoactive medication; serious illness; HT; DM * Base population: nr * Age: 10 ‐ 17 years * Male 57% * Race: nr * Height (mean): nr *Weight (mean): nr * BMI (mean): 22 kg/m² * LDL‐C (mean): 5.4 mmol/L
Interventions	* Treatment: simvastatin 40 mg daily (n = 101); started with 10 mg, doubled at every 8 weeks up to 40 mg * Control: placebo (n = 64) * Run‐in: diet + placebo for 4 weeks * Diet: nr
Outcomes	LDL‐C: enzymatic method TC: enzymatic method HDL‐C: enzymatic method TG: enzymatic method FMD: on brachial artery by ultrasonography, method described (on subset of Dutch group) CRP method: nr ASAT method: nr ALAT method: nr CK method: nr Puberty: Tanner staging by clinical examination Myopathy: criteria nr Adverse events: drug‐related clinical adverse event, criteria unclear, method: nr
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Described as randomized, process not reported.
Allocation concealment (selection bias)	Unclear risk	nr
Blinding (performance bias and detection bias) All outcomes	Low risk	Double blind
Incomplete outcome data (attrition bias) All outcomes	Low risk	Compliance: nr Dropout: 6% Losses to follow‐up: 6% Missing from analysis: 6%
Selective reporting (reporting bias)	Unclear risk	No indication to suspect selective reporting.