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

Stein, Evan A.; Dann, Eldad J.; Wiegman, Albert; Skovby, Flemming; Gaudet, Daniel; Sokal, Étienne; Charng, Min‐Ji; Mohamed, Mafauzy; Luirink, Ilse K.; Raichlen, Joel S.; Sundén, Mattias; Carlsson, Stefan; Raal, Frederick J.; Kastelein, John J.P.

doi:10.1016/j.jacc.2017.06.058

Cited by 47 publications

(36 citation statements)

References 14 publications

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“…10,38 Moreover, the effectiveness of LA in our study is well emphasized by an incidence of CVD (22.2%) and death (16.7%) in the Roman cohort, which is more favorable than other published studies from Europe and South Africa 1,14,[22][23][24] initiated as early as possible. The first ever pediatric randomized trial with hoFH patients was recently published, 39 demonstrating safe and effective use of Rosuvastatin 20 mg (6 weeks crossover), alone or in conjunction with ezetimibe and/or LA. However, longer-term efficacy and safety data are required, particularly in a condition such as hoFH where lifetime therapy is necessary.…”

Section: Discussionmentioning

confidence: 99%

A cross-national investigation of cardiovascular survival in homozygous familial hypercholesterolemia: The Sino-Roman Study

Stefanutti

Pang

Giacomo

et al. 2019

Journal of Clinical Lipidology

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BACKGROUND: Homozygous familial hypercholesterolemia (hoFH) is a rare inherited disorder characterized by extreme elevation of low-density lipoprotein (LDL) cholesterol, accelerated coronary artery disease, and premature death. Aggressive LDL-lowering therapies are important for survival, but these are not available worldwide. OBJECTIVE: The aim of the study was to compare and contrast cardiovascular outcomes and mortality of hoFH patients in 2 countries with disparate use of lipoprotein apheresis (LA) and modern therapies for lowering LDL cholesterol. METHODS: A retrospective study was undertaken comparing cardiovascular disease (CVD)-free survival and mortality in 44 hoFH patients who were treated with statins but not LA, from a center in Beijing, China, and 18 hoFH patients who were treated with LA and novel therapies from an early age, from a center in Rome, Italy. RESULTS: CVD-free survival and survival were significantly reduced in Chinese patients compared with the Italian patients after 30 years of follow-up (log-rank P , .01). In a pooled analysis,

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Section: Discussionmentioning

confidence: 99%

A cross-national investigation of cardiovascular survival in homozygous familial hypercholesterolemia: The Sino-Roman Study

Stefanutti

Pang

Giacomo

et al. 2019

Journal of Clinical Lipidology

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“…In all trials studying efficacy and/or safety, children enrolled were generally 8 years old and above, except for some studies that lowered the age range to reach 4 year olds for simvastatin, 21 5 years old for atorvastatin, 22 and 6 year olds for rosuvastatin, 3 atorvastatin, 4 and pitavastatin. 23 All of these studies had not reported any safety issues or discontinuations, and if present, they were not related to any adverse side effect encountered.…”

Section: Resultsmentioning

confidence: 99%

“…1,2 This would make it difficult somehow for distinctive diagnosis. Fortunately, familial hypercholesterolemia (FH) (homozygous subtype is more aggressive and dangerous but less prevalent than the heterozygous subtype with 1/300,000 to 1/1,000,000 and 1/250 respective ratios 3,4 ) is easily detected both clinically and by blood tests, where average untreated low-density lipoprotein cholesterol (LDL-C) in heterozygous and homozygous subtypes is 140 mg/dL and > 500 mg/dL, respectively, excluding secondary causes of dyslipidemia for the patients' diagnosis. 5 Cardiovascular disease (CVD) is a devastating disease of rapidly increasing prevalence nowadays, whereby it affects 41.5% of the U.S. population, among which 7% are suffering from coronary heart disease where dyslipidemia is one of its main causes.…”

Section: Introductionmentioning

confidence: 99%

Safety of Prescribing Statins in Childhood Dyslipidemia

Al‐Alaili

Abdi

Başgut

2020

Journal of Child Science

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Hyperlipidemia is on the rise in pediatrics, leading to early coronary artery disease complications. Familial hypercholesterolemia is an important risk factor, with the homozygous subtype being more dangerous, yet less prevalent than the heterozygous subtype. Statins are shown to be an effective treatment in this population. This systematic review will emphasize the safety of such drug class in pediatrics, while taking into consideration the latest cholesterol guideline. Cochrane Library, Clinicaltrials.gov, and PubMed were reviewed systematically in June 2019 and rechecked in November 2019 for the past 5 years with keywords like child, safety, hyperlipidemia, and statins, which resulted in nine randomized clinical trials. In short, statins are shown to be intermediately effective—median decrease of low-density lipoprotein cholesterol was 32% achieving the target of < 160 mg/dL in 67% of patients—in lowering lipid levels yet preventing early complications. They are also considered safely tolerated in most cases, even when taken for extended periods, but still not evidently permissible for children below 8 years old, which was the average age of all participants in the trials. Statins should not be given generally for pediatrics of less than 8 years old, in contrast to what was mentioned in the American Heart Association guideline (0–19 age range), since there is no evidence supporting their safety within this age group.

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“…Our observations in one patient suggest that statins could be a promising treatment for plantar keratoderma and associated pain in PC. The long‐term use of statins, and rosuvastatin in particular, has been reported to be safe in familial hypercholesterolaemia, and they do not demonstrate a reduction in efficacy over time . It is possible that statins could effectively alleviate the main symptoms of PC that impact patients’ quality of life but the efficacy and long‐term safety of statin use in the treatment of PC needs to be demonstrated in future clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Pachyonychia congenita: a case report of a successful treatment with rosuvastatin in a patient with a KRT6A mutation

et al. 2018

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Summary Pachyonychia congenita (PC) is a rare autosomal dominant disorder characterized by nail dystrophy and palmoplantar keratoderma with severe plantar pain affecting quality of life. There is no effective treatment. Heterozygous mutations in the keratin genes KRT6A, KRT6B, KRT6C, KRT16 and KRT17 have been reported as a cause of PC. Herein we present a female patient with an amino acid substitution mutation in KRT6A (c.1381G>A, p.Glu461Lys in exon 7) and classic features of PC associated with oral leucokeratosis and follicular hyperkeratosis. We also demonstrate successful treatment of the patient with rosuvastatin. A 3.6‐mm reduction in plantar callosity thickness was demonstrated by sonography. Our patient also experienced significant pain relief that allowed her to increase physical activity (Children's Dermatology Life Quality Index score dropped nine points following treatment). Collectively, these improvements suggest that rosuvastatin may offer a promising treatment for PC. What's already known about this topic? Pachyonychia congenita (PC) is an autosomal dominant disease characterized by nail dystrophy and painful plantar keratoderma. Keratolytics, emollients, retinoids and steroids have been used for treatment but with limited benefits. What does this study add? A patient with PC who had a KRT6A mutation was treated with rosuvastatin with significant improvement in plantar hyperkeratosis and pain. Statins could be a promising treatment for PC with long‐term safety, but further studies are needed.

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

Cited by 47 publications

References 14 publications

A cross-national investigation of cardiovascular survival in homozygous familial hypercholesterolemia: The Sino-Roman Study

A cross-national investigation of cardiovascular survival in homozygous familial hypercholesterolemia: The Sino-Roman Study

Safety of Prescribing Statins in Childhood Dyslipidemia

Pachyonychia congenita: a case report of a successful treatment with rosuvastatin in a patient with a KRT6A mutation

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