Real-World Efficacy and Tolerability of Statins in Children with Familial Hypercholesterolemia: Insights from the VRONI Study

R. S. Schmieder (München)¹, J. Krefting (München)², L. D. Schlieben (München)³, S. Arens (Hannover)⁴, O. Kordonouri (Hannover)⁵, M. Sander (München)⁶, S. Holdenrieder (München)⁷, W. Koenig (München)¹, G. Leipold (Regensburg)⁸, H. Prokisch (München)³, H. Schunkert (München)¹, V. Sanin (München)^9
1Deutsches Herzzentrum München Klinik für Herz- und Kreislauferkrankungen München, Deutschland; ²Deutsches Herzzentrum München Klink für Herzkreislauferkrankungen München, Deutschland; ³Technical University of Munich Institute of Human Genetics - School of Medicine München, Deutschland; ⁴Kinderkrankenhaus auf der Bult Allgemeine Kinderheilkunde, Diabetologie, Endokrinologie, Klinische Forschung, Kindergastr Hannover, Deutschland; ⁵Ärztliche Direktorin Kinder- und Jugendkrankenhaus AUF DER BULT Hannover, Deutschland; ⁶Deutsches Herzzentrum München, TUM Universitätsklinikum München, Deutschland; ⁷Deutsches Herzzentrum München Institut für Laboratoriumsmedizin München, Deutschland; ⁸Regensburg, Deutschland; ⁹Deutsches Herzzentrum München Erwachsenenkardiologie München, Deutschland

Introduction:
Familial hypercholesterolemia (FH) is a common monogenic disorder that causes elevated LDL cholesterol (LDL-C) from childhood onwards, leading to premature cardiovascular disease. Although early diagnosis is recommended, there is limited data on the implementation of therapy in children in the real world.

Methods:
In the VRONI study, routine genetic panel testing was performed on children with LDL-C levels of at least 130 mg/dL. In cases of monogenic FH, written recommendations for statin therapy were provided to local paediatricians and families. Follow-up data was collected via questionnaires completed by attending physicians, focusing on therapy status and LDL-C response. To ensure uniform calculation, statin equivalent doses were used according to standard conversion factors.

Results:
Follow-up data were available for 189 children with monogenic FH. The proportion with LLM was 74.1% (140/189), with no difference between those being seen by a paediatrician or a paediatric cardiologist. The cohort taking LLM was older (13.0 vs 12.0 years) and had a higher baseline LDL-C concentration (181.0 vs 162.5 mg/dL, p = 0.007). There were no significant differences with respect to sex, BMI Z-score or lipoprotein(a). Overall, statin therapy resulted in a significant reduction in LDL-C levels and was well tolerated. Rosuvastatin 5 mg was the most used drug (n=69), reducing LDL-C by a median of 37.2% (IQR 26.9-45.2%). Correlation analysis showed a moderate correlation with statin dosage (Pearson r=0.22, p=0.007; Spearman ρ=0.27, p=0.001). Of the 140 children under LLM, ten reported mild, transient side effects while taking LLM, most commonly muscle symptoms. No serious adverse events were reported, and in five of seven cases with transient muscle symptoms, the statin dosage was increased at a later follow-up.

Conclusion:
The treatment of children with monogenic FH is feasible in primary care. Statins were well tolerated and resulted in a substantial reduction in LDL-C already at low dosages in the VRONI cohort. This supports the guideline recommendation for early pharmacological intervention to prevent long-term cardiovascular risk.