Effectiveness and safety of treatment for heterozygous familial hypercholesterolaemia and multifactorial dyslipidaemia in children: an overview of systematic reviews

This overview of systematic reviews (SRs) summarizes evidence on effectiveness and safety of treatment for paediatric heterozygous familial hypercholesterolaemia (heFH) and multifactorial dyslipidaemia (MFD).

MEDLINE, EMBASE, Cochrane, and Epistemonikos were systematically searched for relevant SRs of randomized controlled trials (RCTs) published 01.01.2015-16.05.2024, with updated search until 31.01.2025. Systematic reviews on different therapeutic interventions assessing surrogate and long-term health outcomes were eligible. AMSTAR-2 was used to appraise SRs and GRADE to evaluate certainty of evidence (CoE). Eight SRs were included and high-quality ones prioritized for further analysis. Among children with heFH, in a meta-analysis of six RCTs (n = 669), statins significantly reduced cholesterol levels compared with placebo over a 2-year follow-up (mean difference, MD: −32.15%; 95% confidence interval, CI: −34.9; −29.4 for LDL-cholesterol; moderate CoE). Significant reductions in LDL-cholesterol levels were also observed for ezetimibe (1 RCT, n = 127; MD: −63 mg/dL; 95% CI: −79.5; −46.5) and PCSK9 inhibitors, with MD in change of −43.3% to −33.8% for evolocumab (1 RCT, n = 157) and alirocumab (1 RCT, n = 153), respectively (moderate CoE). Bile acid sequestrants and fibrates showed significant lipid-lowering effects; however, CoE was low/very low. No significant differences in adverse events during short-term follow-up were observed between study groups for all drugs. Non-pharmacological interventions mainly did not improve lipid profile in paediatric FH (CoE very low). Among children with MFD, behavioural counselling demonstrated modest lipid-lowering effects that attenuated overtime (2 RCTs; low CoE).

In summary, statins are effective lipid-lowering therapy in paediatric FH, with long-term safety requiring further investigation. Evidence evaluating non-pharmacological interventions for childhood dyslipidaemia is sparse.