Knipscheer 1996

Methods	* Design: RCT * Randomization: stratified * Blinding: double * Concealment of allocation: nr * Setting: no. of medical centers nr * Country: Netherlands * Follow‐up: 12 weeks
Participants	Individuals with HeFH (N = 72) * Diagnosis: LDL‐C > 95th percentile on diet and HC or early AS in family * Inclusion: age 8 ‐ 16 years; HeFH ˜ LDL‐C > 95th %tile on diet; HC or early AS in family * Exclusion: major surgery within 3 months; drugs interfering with lipid metabolism; liver or renal dysfunction * Base population: nr Age: 8 ‐ 16 years Male: 35% Race: 92% Height (mean): nr Weight (mean): 47 kg BMI (mean): nr LDL‐C (mean): 6.5 mmol/L
Interventions	* Treatment: pravastatin in 3 treatment arms (n = 53), 5 mg daily (n = 17?), 10 mg daily (n = 18?) and 20 mg daily (n = 18?) * Control: placebo (n = 18) * Run‐in: diet + placebo for 8 weeks * Diet: lipid‐lowering diet, pre‐study diet evaluated with 5 day dietary recall
Outcomes	LDL‐C: enzymatic method, Friedewald's formula TC: enzymatic method HDL‐C: enzymatic method TG: enzymatic method ASAT: routine biochemistry ALAT: routine biochemistry CK: routine biochemistry Myopathy: myalgia, recorded by blinded physicians Adverse events: adverse event, recorded by blinded physicians
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Described as stratified but randomization procedure not described.
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	Unclear risk	Compliance: unclear Dropout: nr Losses to follow‐up: 1% Missing from analysis: 1%
Selective reporting (reporting bias)	Unclear risk	No indication to suspect selective reporting.