Management of children with heterozygous familial hypercholesterolaemia worldwide: a meta-analysis.

Aims: Heterozygous familial hypercholesterolaemia (HeFH) is one of the most frequent monogenic disorders in the world, leading to premature atherosclerotic cardiovascular diseases. The aim of this meta-analysis was to evaluate the efficacy and safety of lipid-lowering therapy (LLT) and achievement of low density lipoprotein cholesterol (LDL-C) goal in children with HeFH. Methods and results: The main endpoint was efficacy of goal achievement for LDL-C and other lipid parameters: total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), apolipoprotein B, and lipoprotein(a), and the LLT safety [adverse events (AEs), including endocrine function, and growth indices]. The secondary endpoint was an effect of LLT on attainment of LDL-C goal treatment (<3.5 mmol/L/130 mg/dL). A total of 41 studies with 4667 paediatric patients at mean age 12.08 ± 2.4 years were included. Seventeen reported the efficacy and safety of LLT therapy compared to control, while the remaining assessed LLT through pre- and post-treatment. At median follow-up of 18.8 months, the group on LLT had significantly higher mean reductions of TC, LDL-C, TG, and increased HDL-C compared to control [-1.75 mmol/L (-67.7 mg/dL), -1.84 mmol/L (-71.2 mg/dL), -0.11 mmol/L (-9.74 mg/dL), 0.08 mmol/L (3.1 mg/dL), respectively, Conclusion: Despite the efficacy of LLT in children with HeFH and the low occurrence of discontinuation-related adverse events, achieving LDL-C treatment goals was relatively rare, with large differences between the investigated countries. These results underscore the importance of considering early combination therapy of statins and ezetimibe, and PCSK9 inhibitors (if available) to attain LDL-C goals effectively.