Advances with lipid-lowering drugs for pediatric patients with familial hypercholesterolemia

ABSTRACT

Introduction

Familial hypercholesterolemia (FH) is a frequent genetic disorder characterized by elevated LDL-cholesterol (LDL-C) and early onset of atherosclerosis.

Areas covered

The authors provide an overview of the pediatric FH scenario, with emphasis on the role of statins as the preferred pharmacological therapy, discussing their potential benefits, as well as adverse effects, and the remaining uncertainties about their use in this population. They also comment on other lipid-lowering therapies.

Expert opinion

Statin therapy is recommended after the ages of 8–10 years old for heterozygous FH patients and can reduce LDL-C by 24–50% depending on drug type and dosage. For more severe cases, higher doses and adjuvant therapies like ezetimibe may be necessary and treatment should be started at diagnosis, as is the case of homozygous FH. Statins reduce progression of subclinical vascular disease and may reduce early cardiovascular events. The available evidence indicates safety of statins in children with no apparent harms related to growth, sexual maturation, steroid hormones, glucose levels, cognitive function, or muscle and liver problems, in comparison with placebo. Newer treatments like lomitapide, PCSK9 inhibitors, bempedoic acid and evinacumab need to be adequately evaluated in pediatric FH patients with more severe dyslipidemia.

KEYWORDS:

• Statins
• familial hypercholesterolemia
• atherosclerosis
• pediatric
• coronary heart disease
• cholesterol

Article Highlights

• Familial hypercholesterolemia (FH) affects approximately 1/310 individuals and is associated with early-onset atherosclerosis.

• FH pediatric patients are born with high LDL-cholesterol and have a greater risk of early cardiovascular disease in comparison with normolipidemic subjects.

• Statins are the mainstay of pharmacological treatment and are well tolerated in pediatric FH.

• Statins reduce progression of subclinical atherosclerosis in pediatric patients and may prevent cardiovascular disease in early adulthood.

• Ezetimibe adds further LDL-cholesterol lowering to statins and has good tolerability.

• Evolocumab a monoclonal antibody against PCSK9 was efficacious and well tolerated in a short-term study and further data are necessary for this class of drugs.

• In homozygous FH, pharmacological treatment must be started at diagnosis and in heterozygous FH at ages 8-10 years old.

Declaration of interest

RD Santos has received honoraria related to consulting, research and/or speaker activities from: Ache, Amgen, AstraZeneca, EMS S.A., Esperion, Kowa, Libbs, Novo Nordisk, Merck and Co., Merck Sharp and Dohme, Pfizer, PTC and Sanofi/Regeneron; VZ Rocha has received honoraria related to speaker activities from: Ache, Amgen, Novo Nordisk and Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.