Statin treatment effective in pediatric patients with homozygous FH

Efficacy of Rosuvastatin in Children With Homozygous Familial Hypercholesterolemia and Association With Underlying Genetic Mutations

Literature - Stein EA, Dann EJ, Wiegman A, et al. - J Am Coll Cardiol. 2017;70(9):1162-1170


Rosuvastatin reduces significantly LDL-C levels in adults with homozygous familial hypercholesterolemia (HoFH), but data in pediatric patients are limited [1]. There is also a lack of data regarding the use of lomitapide, mipomersen and evolocumab, as well as apheresis in young HoFH children [2,3].

In this global study, the efficacy and safety of rosuvastatin on LDL-C and other lipids, lipoproteins, and apolipoproteins was evaluated compared with placebo, in 13 children and adolescents aged < 18 years with HoFH. Moreover, the association between HoFH genotypes and the LDL-C response to rosuvastatin was assessed in a broader HoFH population of both children and adults.

Patients with at least 1 of the following were eligible for the study:

  • genetic confirmation of 2 mutated alleles of either the LDLR, apo B, or PCSK9 genes
  • phenotype with untreated LDL-C >500 mg/dL and triglycerides <400 mg/dL and 1 or more of the following

- tendon or cutaneous xanthoma before the age of 10 years

- HeFH diagnosed by genetic or clinical criteria in both parents

Eligible patients discontinued all lipid-lowering therapy except ezetimibe and/or apheresis, and received rosuvastatin 10 mg daily for 4 weeks in the lead-in phase. Subsequently, they were randomized 1:1 to a double-blind, 12-week crossover period of rosuvastatin 20 mg daily versus placebo, followed by a 12-week, open-label rosuvastatin 20 mg maintenance phase.

Main results

  • Mean ± SD LDL-C level on placebo was 481 ± 185 mg/dL, whereas mean LDL-C on rosuvastatin 20 mg was 396 ± 196 mg/dL, representing a mean absolute reduction in LDL-C of 85.4 mg/dL and a least-squares mean relative difference versus placebo of -22.3% (95% CI: -33.5% to -9.1%; P = 0.005).
  • During the maintenance period, the least-squares mean reduction in LDL-C was 19.3% (P = 0.009).
  • Reductions in apoB, and other apoB-containing lipoproteins, paralleled those for LDL-C, with mean absolute reductions of 33 mg/dL (17.1%) in apoB (P = 0.024) and 93.2 mg/dL (22.9%) in non-HDL-C (P = 0.003).
  • Mean absolute reductions in triglycerides of 39.6 mg/dL (30.4%; P = 0.004) were seen with rosuvastatin 20 mg compared with placebo.
  • Non-statistically significant increases in HDL-C of 1.8 mg/dL (7.4%; P = 0.314) occurred with rosuvastatin 20 mg versus placebo during the crossover phase together with a nominally significant 11.2% increase during the maintenance phase (P = 0.026).
  • The largest mean reductions in LDL-C with rosuvastatin were seen in the subgroup with the most residual LDLR activity, that is, in those with 2 defective LDLR mutations: 23.5% (P = 0.0044) and 21.3% (P = 0.0001) in the children and all patients, respectively.
  • The subgroup with 1 defective and 1 negative mutation in the LDLR demonstrated a mean reduction in LDL-C of 17.0% (P = 0.014).
  • The lowest reductions in LDL-C were seen in the subgroup with 2 negative LDLR mutations: 12.9% (P = 0.022) and 14.0% (P = 0.038) in the children and all patients, respectively.
  • Rosuvastatin 20 mg daily was well tolerated, with no patient terminating the trial. There were neither drug discontinuations due to treatment-related adverse events, nor serious adverse events.


In children and adolescents with HoFH, rosuvastatin 20 mg alone or in combination with ezetimibe and/or apheresis led to an effective LDL-C reduction, and was well tolerated. Consequently, rosuvastatin is approved for the treatment of HoFH pediatric patients 7 to 17 years of age. The LDL-C response to rosuvastatin was related to the underlying mutations and was consistent with that seen in adults.


1. Marais AD, Raal FJ, Stein EA, et al. A dose titration and comparative study of rosuvastatin and atorvastatin in patients with homozygous familial hypercholesterolaemia. Atherosclerosis 2008;197:400–6.

2. Rader DJ, Kastelein JJ. Lomitapide and mipomersen: two first-in-class drugs for reducing low density lipoprotein cholesterol in patients with homozygous familial hypercholesterolemia. Circulation 2014;129:1022–32.

3. Raal FJ, Honarpour N, Blom DJ, et al., TESLA Investigators, for the TESLA investigators. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet 2015;385:341–50.

Find this article online at JACC

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