| Methods | * Design: RCT * Randomization computer‐generated in blocks of 8 * Blinding: double * Compliance monitored by tablet counting * Concealment of allocation: nr * Setting: 1 medical center * Country: Netherlands * Follow‐up: 104 weeks |
|
| Participants | * Participants with HeFH (N = 214) * Diagnosis: molecular diagnosis in parent and LDL‐C > 4.0 mmol/L * Inclusion: age 10 ‐ 17 years; female; 1 parent with FH and LDL‐C 4.1‐10.3 mmol/L on diet; TG < 4.0 mmol/L; postmenarchal > 1 year * Exclusion: pregnancy; under/overweight; HoFH; dyslipidaemia I, III‐V; DM, hypothyroidism; renal disorder; certain medication (immunosuppressants, corticosteroids, cytochrome P‐450 inhibitors) * Base population: unclear; 81 participants were screened * Age: 8 ‐ 18 years * Male: 47% * Race: nr * Height (mean): 157 cm * Weight (mean): 49 kg * BMI (mean): 20 kg/m² * LDL‐C (mean): 6.2 mmol/L | |
| Interventions | * Treatment: pravastatin 20 to 40 mg daily in the evening depending on age (n = 104) * Control: placebo (n = 107) * Run‐in: fat‐restricted diet * Diet: fat‐restricted diet; 7 d dietary records; evaluated | |
| Outcomes | LDL‐C: enzymatic method, calculated Friedewald's formula TC: enzymatic method HDL‐C: naheparin‐manganese chloride method TG: enzymatic method ALAT: > 3 x ULN, analysis method: nr ASAT: > 3 x ULN, analysis method: nr CPK: > 4 x ULN, analysis method: nr IMT: ultrasonography; method described Puberty: Tanner staging, clinical examination | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated in blocks of 8. |
| 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: unclear Dropout: 5% Losses to follow‐up: 1% Missing from analysis: 1% |
| Selective reporting (reporting bias) | Unclear risk | No indication to suspect selective reporting. |
AHA: American Heart Association ALAT: alanine amino transferase ASAT: aspartate amino transferase BMI: body mass index CAD: coronary artery disease CK: creatine kinase CRP: C‐reactive protein CVD: cardiovascular disease DM: diabetes mellitus FH: familial hypercholesterolemia FMD: flow‐mediated dilatation HC: hypercholesterolemia HDL‐C: high‐density lipoprotein cholesterol HeFH: heterozygous familial hypercholesterolemia HoFH: homozygous familial hypercholesterolemia HT: hypertension IMT: intima‐media thickness LDL‐C: low‐density lipoprotein cholesterol NCEP: National Cholesterol Education Panel nr: not reported RCT: randomized controlled trial TC: total cholesterol TG: triglycerides ULN: upper limit of normal