Multimodal lipid-lowering treatment in pediatric patients with homozygous familial hypercholesterolemia—target attainment requires further increase of intensity

Klaus, Günter; Taylan, Christina; Schmitt, Claus Peter; Pape, Lars; Oh, Jun; Driemeyer, Joenna; Galiano, Matthias; König, Jens; Schürfeld, Carsten; Spitthöver, Ralf; Schaefer, Juergen R.; Weber, Lutz T.; Heibges, Andreas; Klingel, Reinhard

doi:10.1007/s00467-018-3906-6

Cited by 14 publications

(6 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data demonstrate that early efficacious treatment remains the key to prevent CVD and death in hoFH patients. Despite starting apheresis at a mean of 9 years and lomitapide at a mean of 24 years, the 17% mortality rate of hoFH on LA in the present study, consistent with previous observational studies, 41,42 shows that LA delays the development of atherosclerosis but does not completely arrest progression. 14,43 Ultimately, with the advent of new therapies such as PCSK9 inhibitors and angiopoietin-like protein 3 inhibitors, 44 there is hope on the horizon for individuals with hoFH if these treatments, combined with LA, 29 are instituted early enough.…”

Section: Discussionsupporting

confidence: 91%

A cross-national investigation of cardiovascular survival in homozygous familial hypercholesterolemia: The Sino-Roman Study

Stefanutti

Pang

Giacomo

et al. 2019

Journal of Clinical Lipidology

View full text Add to dashboard Cite

BACKGROUND: Homozygous familial hypercholesterolemia (hoFH) is a rare inherited disorder characterized by extreme elevation of low-density lipoprotein (LDL) cholesterol, accelerated coronary artery disease, and premature death. Aggressive LDL-lowering therapies are important for survival, but these are not available worldwide. OBJECTIVE: The aim of the study was to compare and contrast cardiovascular outcomes and mortality of hoFH patients in 2 countries with disparate use of lipoprotein apheresis (LA) and modern therapies for lowering LDL cholesterol. METHODS: A retrospective study was undertaken comparing cardiovascular disease (CVD)-free survival and mortality in 44 hoFH patients who were treated with statins but not LA, from a center in Beijing, China, and 18 hoFH patients who were treated with LA and novel therapies from an early age, from a center in Rome, Italy. RESULTS: CVD-free survival and survival were significantly reduced in Chinese patients compared with the Italian patients after 30 years of follow-up (log-rank P , .01). In a pooled analysis,

show abstract

Section: Discussionsupporting

confidence: 91%

A cross-national investigation of cardiovascular survival in homozygous familial hypercholesterolemia: The Sino-Roman Study

Stefanutti

Pang

Giacomo

et al. 2019

Journal of Clinical Lipidology

View full text Add to dashboard Cite

show abstract

“…With a combined therapy with drugs and LA, only three of 17 patients were able to achieve a mean LDL plasma concentration below the pediatric target value of 135 mg/dL. In only two of 17 patients, the frequency of LA was twice a week, and notably, these two children reached target values [ 31 ]. Increasing the LA frequency to twice a week can further reduce mean LDL and has been shown to be more effective when compared to increasing treated plasma volume [ 32 ].…”

Section: Lipid Apheresis In Childrenmentioning

confidence: 99%

An update on lipid apheresis for familial hypercholesterolemia

Taylan

Weber

2022

Pediatr Nephrol

Self Cite

View full text Add to dashboard Cite

Familial hypercholesterolemia (FH) is an inherited metabolic defect leading to increased total cholesterol and low-density cholesterol (LDL) from birth onwards. Homozygous FH, presenting with clear clinical features, has a prevalence of ~ 1 per million. Prevalence of heterozygous FH is 1/500 European population. Atherosclerotic burden depends on the degree and duration of high LDL exposure. In severe cases, early detection is critical, and aggressive lipid-lowering therapies should begin in early childhood to reduce coronary heart disease risk. Pediatric therapeutic concepts correspond to adults and are orientated at LDL plasma concentration. Mean LDL plasma target value during treatment is < 135 mg/dL. Medication in childhood consists of ezetemibe, statins, resins, and PCSK-9 inhibitors, with consideration for age restrictions. Only a minority achieve the treatment target with drug therapy alone. Therapeutic apheresis for the treatment of hypercholesterolemia selectively removes lipoproteins from blood (lipid apheresis (LA)). LA has a long tradition in adult medicine and is also safely used in children by a variety of methods, if customized to special pediatric needs. LA reduces cholesterol levels independently of residual LDL-receptor function and not only achieves reduction or disappearance of xanthomas but also inhibits progression of or mitigates aortic valve stenosis and supravalvular aortic stenosis as well as coronary artery and other atherosclerotic lesions. Cardiovascular prognosis of patients with otherwise untreatable FH depends largely on timely use of LA. Taking into account LA as a lifelong treatment, starting early in childhood, it is important to accommodate therapy modalities, such as treatment frequency and point of time, into the life of the individual.

show abstract

“…LA is a complex treatment for patients and their families, indeed. However, in our knowledge, LA was not associated with impairment of health-related quality of life [ 71 ]. In a very recent study (2020), the authors set a database on therapeutic characteristics and outcomes of a group of HoFH patients who have been submitted to LA during their childhood.…”

Section: Lipoprotein Apheresismentioning

confidence: 99%

Current Approach to the Diagnosis and Treatment of Heterozygote and Homozygous FH Children and Adolescents

Cohen

Stefanutti²

2021

Curr Atheroscler Rep

View full text Add to dashboard Cite

Purpose of Review To elucidate the current approach of care in pediatric patients with familial hypercholesterolemia (FH). We sought an answer to the question whether the advances and major changes in lipid management are relevant and apply to children and adolescents. Recent Findings Latest research findings clearly demonstrate that lowering cholesterol levels at a young age prevents vascular atherosclerotic changes and decreases cardiovascular events in adulthood and emphasizes the importance of early detection and intervention in the pediatric FH patients group. Summary FH is a common genetic disease caused by mutations in genes associated with the metabolism of low-density lipoproteins (LDL). The hallmark of FH is elevated LDL cholesterol (LDL-C) levels from birth and premature atherosclerotic cardiovascular disease (ASCVD). Often FH is either undiagnosed or diagnosed with a considerable delay, leading to vascular atherosclerotic changes and cardiovascular disease. Prompt identification of FH subjects is essential, to initiate early preventive measures. Safe and efficient pharmacological agents are approved for use in children and adolescents. Statins are the first line of therapy, in combination of ezetimibe. Unfortunately, these drugs do not warrant the achievement of therapeutic target, especially in HoFH patient. In the latter, lipoprotein apheresis (LA), which has been shown to be safe and effective, is strongly recommended. Finally, the new drugs still under study will allow a multimodal customized treatment. Lowering cholesterol levels at a young age hinders vascular atherosclerotic changes decreasing cardiovascular events in adulthood. Therefore, early detection, diagnosis, and intervention in FH patients are priority objectives.

show abstract

Multimodal lipid-lowering treatment in pediatric patients with homozygous familial hypercholesterolemia—target attainment requires further increase of intensity

Cited by 14 publications

References 43 publications

A cross-national investigation of cardiovascular survival in homozygous familial hypercholesterolemia: The Sino-Roman Study

A cross-national investigation of cardiovascular survival in homozygous familial hypercholesterolemia: The Sino-Roman Study

An update on lipid apheresis for familial hypercholesterolemia

Current Approach to the Diagnosis and Treatment of Heterozygote and Homozygous FH Children and Adolescents

Contact Info

Product

Resources

About