Real-world efficacy and tolerability of lipid-lowering therapy in children with monogenic familial hypercholesterolemia in primary care

Background/Introduction Familial hypercholesterolaemia (FH) is characterised by elevated LDL-C levels from an early age and confers a high risk of premature cardiovascular disease. Although guidelines recommend the early initiation of lipid-lowering medication (LLM) following an FH diagnosis, there is limited data on the uptake, effectiveness and tolerability of treatment in paediatric primary care. Purpose To evaluate the initiation, efficacy and safety of LLM in children with monogenic FH who were identified through a FH screening programme. Methods Children with LDL-C levels of at least 130 mg/dL underwent routine genetic panel testing as part of a FH screening study. Those with monogenic FH received written recommendations for statin therapy, which were provided to local paediatricians and families. Referral to paediatric cardiologists was at the discretion of the local paediatrician. Follow-up data were collected via physician questionnaires assessing therapy status and LDL-C response. Statin doses were standardised using equivalent dose calculations. Results Follow-up data were available for 215 children, of whom 68% were treated by local paediatricians and 32% by paediatric cardiologists. Overall, 79% (171/215) of children received LLM, with no significant difference between the two groups. Children who were treated had higher baseline LDL-C levels (median 181.0 vs. 162.5 mg/dL, p = 0.007) and were older (13.0 vs. 10.0 years). No differences were observed for lipoprotein(a) or BMI z-score. Of the 150 complete therapy frames analysed (i.e. with data on LDL-C at least four weeks after LLM initiation), LDL-C lowering was moderately dose-dependent (Pearson r = 0.22, p = 0.007; Spearman ρ = 0.27, p = 0.001). Rosuvastatin was the most frequently used statin (89%), with a daily dose of 5 mg reducing LDL-C by 37.2% (IQR 26.9–45.2). Mild transient adverse events occurred in nine children taking statins, with therapy being reinstated after a short pause and statin dosage being increased later on. There was also one case of transient headaches with ezetimibe. No serious adverse events were reported. Conclusions LLM can be safely and effectively administered in primary care for children with monogenic FH and already low-dose statins resulted in substantial LDL-C reduction. Overall, this demonstrates real world applicability of guideline recommendations for early start of treatment in FH in a primary care setting.