McCrindle 2003

Methods	* Design: RCT * Randomization process: nr * Blinding: double * Concealment of allocation: nr * Setting: 20 medical centers (6 USA, 5 Canada, 8 Europe, 1 South Africa) * Country: USA, Canada, Ireland, France, Spain, England, Sweden, Norway, South Africa * Follow‐up: 26 weeks
Participants	* Individuals with HeFH (N = 187) * Diagnosis: FH or severe hypercholesterolemia and LDL‐C > 4.9 mmol/L OR LDL‐C > 4.1 mmol/L and family history of FH OR LDL‐C > 4.1 mmol/L and premature CHD in 1°/2° relatives * Inclusion: age 10 ‐ 17 years; HeFH or LDL‐C ≧ 4.9 mmol/L or LDL‐C ≧ 4.1 mmol/L with HC or early AS in family; Tanner ≧ II; LDL‐C ≧ 4.1 mmol/L w/ diet during baseline phase * Exclusion: premenarche; pregnancy; under or overweight; liver or kidney disorder; HoFH; other clinical trial; hypersensitivity to statins * base population: nr Age: 10 ‐ 17 years Male: 69% Race: 92% white Height (mean): nr Weight (mean): nr BMI (mean): nr LDL‐C (mean): 5.7 mmol/L
Interventions	* Treatment: atorvastatin 10 ‐ 20 mg daily (n = 140); median 20 mg, increased to 20 mg if LDL‐C ≧ 3.4 mmol/L at 4 weeks * Control: placebo (n = 47) * Run‐in: washout for 4 weeks before the trial; placebo/diet run‐in for 4 weeks * Diet: NCEP step 1 diet; instructions in the beginning of the study
Outcomes	LDL‐C: samples analyzed centrally TC: samples analyzed centrally HDL‐C: samples analyzed centrally TG: samples analyzed centrally ALAT: >3 x ULN samples analyzed in a routine manner ASAT: >3 x ULN samples analyzed in a routine manner Puberty: increase in Tanner staging ≧ 1, clinical examination Adverse event: self‐report or detected by the investigator
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: 2% Losses to follow‐up: 0% Missing from analysis: 0%
Selective reporting (reporting bias)	Unclear risk	No indication to suspect selective reporting.