Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Risk Factors for Morbidity and Mortality Following Hospitalization for Pericarditis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Long-Term Adverse Cardiac Outcomes in Patients With Sarcoidosis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Smartphone Activation of Citizen Responders to Facilitate Defibrillation in Out-of-Hospital Cardiac Arrest

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Obesity as a Causal Risk Factor for Aortic Valve Stenosis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Danish expanded newborn screening is a successful preventive public health programme

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. The impact of consanguinity on the frequency of inborn errors of metabolism

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Exome sequencing for syndrome diagnostics

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Arvelige neurometaboliske sygdomme

    Publikation: Bidrag til bog/antologi/rapportBidrag til bog/antologiUndervisning

  • Evan A Stein
  • Eldad J Dann
  • Albert Wiegman
  • Flemming Skovby
  • Daniel Gaudet
  • Etienne Sokal
  • Min-Ji Charng
  • Mafauzy Mohamed
  • Ilse Luirink
  • Joel S Raichlen
  • Mattias Sundén
  • Stefan C Carlsson
  • Frederick J Raal
  • John J P Kastelein
Vis graf over relationer

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder, is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerotic cardiovascular disease. Statin treatment starts at diagnosis, but no statin has been formally evaluated in, or approved for, HoFH children.

OBJECTIVES: The authors sought to assess the LDL-C efficacy of rosuvastatin versus placebo in HoFH children, and the relationship with underlying genetic mutations.

METHODS: This was a randomized, double-blind, 12-week, crossover study of rosuvastatin 20 mg versus placebo, followed by 12 weeks of open-label rosuvastatin. Patients discontinued all lipid-lowering treatment except ezetimibe and/or apheresis. Clinical and laboratory assessments were performed every 6 weeks. The relationship between LDL-C response and genetic mutations was assessed by adding children and adults from a prior HoFH rosuvastatin trial.

RESULTS: Twenty patients were screened, 14 randomized, and 13 completed the study. The mean age was 10.9 years; 8 patients were on ezetimibe and 7 on apheresis. Mean LDL-C was 481 mg/dl (range: 229 to 742 mg/dl) on placebo and 396 mg/dl (range: 130 to 700 mg/dl) on rosuvastatin, producing a mean 85.4 mg/dl (22.3%) difference (p = 0.005). Efficacy was similar regardless of age or use of ezetimibe or apheresis, and was maintained for 12 weeks. Adverse events were few and not serious. Patients with 2 defective versus 2 negative LDL receptor mutations had mean LDL-C reductions of 23.5% (p = 0.0044) and 14% (p = 0.038), respectively.

CONCLUSIONS: This first-ever pediatric HoFH statin trial demonstrated safe and effective LDL-C reduction with rosuvastatin 20 mg alone or added to ezetimibe and/or apheresis. The LDL-C response in children and adults was related to underlying genetic mutations. (A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia [HYDRA]; NCT02226198).

OriginalsprogEngelsk
TidsskriftJournal of the American College of Cardiology
Vol/bind70
Udgave nummer9
Sider (fra-til)1162-1170
Antal sider9
ISSN0735-1097
DOI
StatusUdgivet - 29 aug. 2017

ID: 52804251