Statin therapy effective and safe in children and adolescents with FH
Efficacy and safety of statin use in children and adolescents with familial hypercholesterolaemia: a systematic review and meta-analysis of randomized-controlled trials
Introduction and methods
Familial hypercholesterolemia (FH) is characterized by elevated LDL-c concentrations and is inherited in an autosomal dominant way [1,2]. Heterozygous FH (HeFH) is characterized by LDL-c concentrations varying between 190 and 500 mg/dL (4.9 – 12.9 mmol/L) and affects ~1:200-1:300 people worldwide. Homozygous FH (HoFH) is rarer (1:160,000 to 1:300,000 individuals), with LDL-c concentrations >500 mg/dL (>12.9 mmol/L) . Prolonged exposure to high LDL-c or other lipids predispose FH patients to an increased risk for CVD from childhood age . Statins are the recommended treatment for children and adults with FH [3-6]. In this study, a systematic review and meta-analysis were performed to evaluate the lipid-lowering efficacy of statins on total cholesterol (TC), LDL-c, triglicerides (TG), HDL-c and apolipoprotein B (apo-B) concentrations in children and adolescents with FH in comparison with placebo. Adverse effects associated with statin use and comparative data concerning dose were also studied.
This study included studies in patients (age range 8-18 years) with FH, according to the Dutch Lipid Clinic Score, the US Make Early Diagnosis to Prevent Early Death or the Simon Broom criteria. The included studies provided extractable data and used statin monotherapy in the intervention group and placebo or diet in the control group. A total of ten randomized clinical trials (RCTs) were included in the qualitative analysis and nine in the quantitative analysis, yielding a total number of 1191 individuals with FH (all with HeFH, mean age was 13.3 ± 2.5 years, ranging from 10.6±2.9 to 15±2 years).
- Compared with placebo, treatment with statins lowered TC, LDL-C, TG and apo-B levels (mean absolute changes for TC: -79.3 mg/dL, 95%CI -93.9 to -64.7, I²=85%; LDL-c: -78.5 mg/dL, 95%CI -93.2 to -63.8, I²=87%; TG: -4.8 mg/dL, 95%CI -9.7 to 0.1, I²=16%; apo-B: -49.6 mg/dL, 95%CI -60.4 to -38.8, I²=86%).
- Mean relative differences in TC, LDL-c, TG and apo-B with statins vs placebo were: -25.5% (95%CI -30.4% to -20.5%, I²=91%) for TC, -33.8% (95%CI -40.1% to -27.4%, I²=90%) for LDL-c, -8.4% (95%CI -14.8% to -2.03%, I²=26%) for TG, and -28.8% (95%CI -33.9% to -23.6%, I²= 83%) for apo-B.
- Treatment with statins raised HDL-c concentration levels, compared to placebo (mean absolute difference: 1.2 mg/dL, 95%CI 0.88 to 2.29, I²=0%); Mean relative difference: 3.1%, 95%CI 1.1 to 5.2, I²=0%).
- Mean relative differences in TC and LDL-c with low-intensity statins vs. placebo were -22.3% (95%CI -27.64% to -16.96%) and -29.70% (95%CI -36.4% to -22.9%), respectively. The respective reduction with moderate-intensity statins was -25.6% in TC (95%CI -30.8% to -20.4%) and -32.78% in LDL-c (95%CI -38.65% to -26.91%). With high-intensity statins, the reductions were -39% in TC (95%CI -43.7% to -34.2%) and -49% in LDL-c (95%CI -55.5% to -42.4%).
- All statins were generally well-tolerated. No differences in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and CK levels were found between statin therapy and placebo. Incidence of adverse events (AEs) was similar between statin and placebo groups. Treatment-related AEs were similar across treatment groups and ranged from 0-15%. Serious AEs were not related to statin treatment. Discontinuation rates due to AEs ranged from 0% to 0.7-1.9%. No clinical signs of growth or sexual impairment and no change in gonadal steroid concentrations were observed during statin treatment.
Statin treatment in children and adolescents with FH reduces TC, LDL-c and apo-B. A modest reduction in TG concentrations and modest increase in HDL-c levels were also observed. Statin potency appears to have an effect on the lipid-lowering efficacy in this age group. Statins were generally well tolerated and no clinical signs of growth or sexual impairment were observed.