Physicians' Academy for Cardiovascular Education

Initiating statin therapy in children with FH reduces subclinical and clinical atherosclerotic disease

20-Year Follow-up of Statins in Children with Familial Hypercholesterolemia

Literature - Luirink IK, Wiegman A, Kusters DM et al., - N Engl J Med 2019; 381:1547-1556. DOI: 10.1056/NEJMoa1816454

Introduction and methods

Patients with familial hypercholesterolemia (FH) are at high risk for premature CV disease, as a result of elevated LDL-c levels since birth, caused by mutations in genes encoding proteins involved in the LDL receptor metabolism [1]. The first functional and morphologic changes of the arterial wall have been demonstrated to start in childhood [2,3]. An EAS consensus panel and the current ACC/AHA guidelines for FH therefore advise initiation of statins in children aged 8 [4] or 10 [5] years old, respectively.

The lipid-lowering effect of statins in children is well established [6], but good follow-up data on clinical outcomes in treated children are scarce. Also in adults with FH, the benefit of statin treatment in the prevention of CV disease has not adequately been established prospectively.

This study is a 20-year follow-up study of children with genetically defined FH who started statin therapy between the ages of 8 and 18 years old. It aims to study differential progression in both subclinical atherosclerosis and clinical CV disease, and to compare the outcomes between those with FH who started treatment in childhood and those with untreated FH and healthy persons. Subclinical atherosclerosis progression over time was assessed by comparing the carotid intima media thickness (cIMT) in patients with FH with their unaffected age-matched siblings. Follow-up lasted until adulthood, at an age when the affected parents may already have experienced an event. The incidence of CV disease among FH patients was compared with that among their parents with FH, who started statin therapy much later in life.

214 Children with FH who enrolled in a double-blind placebo-controlled trial that evaluated the 2-year efficacy and safety of pravastatin from 1997-1999 [6] were eligible for this study. Moreover, 95 unaffected (confirmed by genetic testing) enrolled at the time as a control group, and they were also eligible now. About 20 years after initial enrollment, patients and their unaffected siblings were contacted again, and those who agreed to participate in the current study answered a questionnaire about medical history, lifestyle habits, medication use and family history, and they visited the clinic once.

Main results


This study shows that 20 years after enrollment in a pediatric statin trial, progression of cIMT in participants with genetically defined FH was similar to that in their unaffected siblings. Patients with FH who were treated since childhood showed a lower cumulative incidence of CV events and CV death than among their affected parents, who initiated statin therapy later in life.


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Find this article online at N Engl J Med

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