Stein 1999

Methods	* Design: RCT * Randomization process: nr * Blinding: double * Concealment of allocation: nr * Setting: 14 pediatric clinics (13 USA, 1 Finland) * Country: USA, Finland * Follow‐up: 24 and 48 weeks
Participants	* Participants with HeFH (N = 132) * Diagnosis: LDL‐C > 4.9mmol/L and 1 parent LDL‐C > 4.9mmol/l; or LDL‐C > 5.7mmol/L and CAD death in 1 parent * Inclusion: age 10 ‐ 17 years; LDL‐C 4.9 ‐ 13.0 mmol/L on diet and ≧ 1 parent with LDL‐C ≧ 4.9 mmol/L with or LDL‐C 5.7 ‐ 13.0 mmol/L on diet and a parent died of CAD; (Tanner > I required later by FDA > 8 participants needed to discontinue) * Exclusion: delayed puberty; under/overweight; HoFH; secondary hyperlipidaemia; TG disorders * Base population: unclear * Age: 11 ‐ 17 years * Male: 100% * Race: 93% * Height (mean): 159 cm * Weight (mean): 52 kg * BMI (mean): 21 kg/m² * LDLC (mean): 6.5 mmol/L
Interventions	* Treatment: lovastatin 40 mg in the evening (n = 63); started with 10 mg, increased to 20/40 mg at weeks 8/16 * Control: placebo (n = 59) * Run‐in: diet for 4 months; placebo run‐in for 4 weeks * Diet: AHA pediatric diet; instructed, monitored and evaluated throughout trial
Outcomes	LDL‐C: enzymatic method TC: enzymatic method HDL‐C: heparin‐manganese chloride method TG: enzymatic method ALAT > 3 x ULN: samples analyzed centrally ASAT > 3 x ULN: samples analyzed centrally CK > 10 x ULN: samples analyzed centrally Myalgia criteria: nr Adverse event: new or worsening clinical adverse event, not otherwise specified
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: 8% Losses to follow‐up: 8% Missing from analysis: 8%
Selective reporting (reporting bias)	Unclear risk	No indication to suspect selective reporting.