ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: N Engl J Med. 2019;381(16):1547–56. doi: 10.1056/NEJMoa1816454

Short summary: Twenty years of treatment of statin therapy in children with Familial Hypercholesterolemia (FH) slowed the progression of carotid intima–media thickness and reduced the risk of cardiovascular disease in adulthood. By age 39 years, the cumulative incidence of cardiovascular disease events in untreated parents with FH was 26% compared with only 1% in treated children.

Comment: FH is an autosomal dominant disorder. Recent genetic epidemiological studies suggest a frequency of about 1 in 250. Coronary atherosclerosis occurs prematurely and lifelong treatment, from early childhood, is needed. In 2008, the American Academy of Paediatrics issued revised recommendations for the management of hypercholesterolemia in children. Within days after publication, the new policy statement had elicited a firestorm of controversy.¹ Questions about the evidence base for statins emerged mainly in regard to the robustness of long-term evidence in children, and the possible harms of statins.

The current study investigated the long-term benefits of initiating early statin therapy in children with FH. The cohort comprised 184 individuals with FH and 77 of their unaffected siblings who were followed for 20 years. Statin therapy in this group was initiated at a mean age 14.0 ± 3.1 years. Overall, 79% of individuals with FH reported continued use of lipid-lowering medication. Their mean LDL-C levels decreased by 32%, from 237 mg/dl at baseline to 161 mg/dl at follow-up. In contrast, in their unaffected siblings, LDL-C levels increased by 24%, from 98 mg/dl to 122 mg/dl. At baseline, mean carotid intima–media thickness was greater in FH children than in their unaffected siblings. However, during the 20-year period, the mean rate of thickening was similar in both groups. Most importantly, by age 39 years, the cumulative incidence of cardiovascular disease events was 26% in the parents and 1% in treated children; death from cardiovascular causes was 7% in parents and 0% in children. No episodes of rhabdomyolysis or other serious adverse events were reported.

These findings support the notion that atherogenesis is the product of both the magnitude and the duration of exposure of the arterial wall to LDL-C, and reinforces clinical guideline recommendations to initiate statin therapy by age 8–10 years in individuals with FH. The authors concluded that this makes a strong case not only for ‘the lower the better’ but also for ‘the younger the better.’

Reference:

1. de Ferranti S, Ludwig DS. Storm over Statins — The Controversy Surrounding Pharmacologic Treatment of Children. 2008;359(13):1309–12. doi: 10.1056/NEJMp0805953.