European journal of preventive cardiology · 2026
Effectiveness and safety of treatment for heterozygous familial hypercholesterolaemia and multifactorial dyslipidaemia in children: an overview of systematic reviews.
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Le Thi Thu Giang, Geist Milena, Novosad Yuliia, Litwin Anna, Gomes Delphina, Grünzner Juliane, Koletzko Berthold, Patro-Golab Bernadeta
Аннотация
AIMS: This overview of systematic reviews (SRs) summarizes evidence on effectiveness and safety of treatment for paediatric heterozygous familial hypercholesterolaemia (heFH) and multifactorial dyslipidaemia (MFD).
METHODS AND RESULTS: 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).
CONCLUSIONS: 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.
METHODS AND RESULTS: 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).
CONCLUSIONS: 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.