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Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Toppari, Jorma / Turan, Serap Demircioglu


IMPACT FACTOR 2018: 1.239

CiteScore 2018: 1.22

SCImago Journal Rank (SJR) 2018: 0.507
Source Normalized Impact per Paper (SNIP) 2018: 0.562

Online
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2191-0251
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Volume 29, Issue 11

Issues

A 10-year experience using combined lipid-lowering pharmacotherapy in children and adolescents

María Beatriz Araujo / María Sol Pacce
Published Online: 2016-10-08 | DOI: https://doi.org/10.1515/jpem-2016-0117

Abstract

Background:

Current pediatric guidelines for heterozygous familial hypercholesterolemia (HeFH) propose pharmacotherapy (PT) with statins from age 8 to 10 years; however, schemes with absorption inhibitors combined with statins, could be started earlier. The aim of the study was to show the 10-year results of a combined treatment protocol.

Methods:

Prospective, descriptive and analytical study. Pediatric patients (n=70; mean age at PT initiation 9.3 years [range, 2–17.5]) with HeFH who required PT between 2005 and 2015 were included. All patients ≥10 years, with LDL >190 mg/dL or >160 mg/dL with one cardiovascular risk factor (CVRF) or >130 mg/dL with two or more CVRF; and those patients 5–10 years and with LDL-C >240 mg/dL or a family history of a cardiovascular event before 40 years, were medicated. After a period on a lipid-lowering diet (LLD), all patients were started on ezetimibe. Patients who did not achieve the treatment goal were given statins. The variables were: age, age at PT initiation, duration of PT, initial LDL-C, mean LDL-C during ezetimibe monodrug therapy, mean LDL-C during combined PT, and percentage of LDL decrease.

Results:

LDL-C levels were: Baseline: 235 mg/dL±55; after 3 months on ezetimibe: 167 mg/dL±47 (decrease: −27.62%). In 18 patients who did not reach the treatment goal atorvastatin was added and their LDL-C decreased −41.5% (p: 0.02). Overall, mean final LDL-C was 155 mg/dL±30.4 (range, 98–257) and treatment goals were reached in 74% of the patients. No severe side effects were reported.

Conclusions:

Combined and sequential treatment starting at early ages was shown to be safe and effective over this follow-up period.

Keywords: ezetimibe; heterozygous familial hypercholestrolemia; pediatrics; pharmacotherapy; statins

References

  • 1.

    Goldstein J, Hobbs H, Brown M. The online metabolic and molecular bases of inherited disease. Chapter 120. Familial hypercholesterolemia. http://ommbid.mhmedical.com/DOI:10.1036/ommbid.149.

  • 2.

    Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science 1986;232:34–47.CrossrefPubMedGoogle Scholar

  • 3.

    Cuchel M, Bruckert E, Ginsberg HN, Raal FJ, Santos RD, et al. European atherosclerosis society consensus panel on familial hypercholesterolaemia. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J 2014;35:2146–57.PubMedWeb of ScienceGoogle Scholar

  • 4.

    Daniels SR, Gidding SS, de Ferranti SD. National lipid association expert panel on familial hypercholesterolemia. Pediatric aspects of familial hypercholesterolemias: recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol 2011;5(Suppl 3):S30–7.Web of ScienceCrossrefGoogle Scholar

  • 5.

    Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk. Reduction in Children and Adolescents; National Heart, Lung, and Blood Institute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics 2011;128(Suppl 5):S213–56.Google Scholar

  • 6.

    Descamps OS, Tenoutasse S, Stephenne X, Gies I, Beauloye V, et al. Management of familial hypercholesterolemia in children and young adults: consensus paper developed by a panel of lipidologists, cardiologists, paediatricians, nutritionists, gastroenterologists, general practitioners and a patient organization. Atherosclerosis 2011;218:272–80.Web of ScienceCrossrefGoogle Scholar

  • 7.

    Myśliwiec M, Walczak M, Małecka-Tendera E, Dobrzańska A, Cybulska B, et al. Management of familial hypercholesterolemia in children and adolescents. Positionpaper of the Polish Lipid Expert Forum. J Clin Lipidol 2014;8:173–80.CrossrefGoogle Scholar

  • 8.

    Kusters DM, Wiegman A, Kastelein JJ, Hutten BA. Carotid intima-media thickness in children with familial hypercholesterolemia. Circ Res 2014;114:307–10.Web of SciencePubMedCrossrefGoogle Scholar

  • 9.

    McNeal CJ, Wilson DP, Christou D, Bush RL, Shepherd LG, et al. The use of surrogate vascular markers in youth at risk for premature cardiovasculardisease. J Pediatr Endocrinol Metab 2009;22:195–211.Google Scholar

  • 10.

    Guardamagna O, Restagno G, Rolfo E, Pederiva C, Martini S, et al. The type of LDLR gene mutation predicts cardiovascular risk in children with familial hypercholesterolemia. J Pediatr 2009;155:199–204.CrossrefPubMedGoogle Scholar

  • 11.

    Choh SA, Choh NA, Rasool A, Yousuf R, Qureshi U. Homozygous familial hypercholesterolemia. J Pediatr Endocrinol Metab 2009;22:573–5.PubMedGoogle Scholar

  • 12.

    Davis HR Jr, Pula KK, Alton KB, Burrier RE, Watkins RW. The synergistic hypocholesterolemic activity of the potent cholesterol absorption inhibitor, ezetimibe, in combination with 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors in dogs. Metabolism 2001;50:1234–41.PubMedCrossrefGoogle Scholar

  • 13.

    Lambert M, Lupien PJ, Gagné C, Lévy E, Blaichman S, et al. Treatment of familial hypercholesterolemia in children and adolescents: effect of lovastatin. Canadian Lovastatin in Children Study Group. Pediatrics 1996;97:619–28.Google Scholar

  • 14.

    McCrindle BW, Helden E, Cullen-Dean G, Conner WT. A randomized crossover trial of combination pharmacologic therapy in children with familial hyperlipidemia. Pediatr Res 2002;51:715–21.PubMedCrossrefGoogle Scholar

  • 15.

    Clauss SB, Holmes KW, Hopkins P, Stein E, Cho M, et al. Efficacy and safety of lovastatin therapy in adolescent girls with heterozygous familial hypercholesterolemia. Pediatrics 2005;116:682–8.CrossrefPubMedGoogle Scholar

  • 16.

    Kusters DM, Hutten BA, McCrindle BW, Cassiman D, Francis GA, et al. Design and baseline data of a pediatric study with rosuvastatin in familial hypercholesterolemia. J Clin Lipidol 2013;7:408–13.CrossrefWeb of SciencePubMedGoogle Scholar

  • 17.

    Kusters DM, Avis HJ, de Groot E, Wijburg FA, Kastelein JJ, et al. Ten-year follow-up after initiation of statin therapy in children with familial hypercholesterolemia. J Am Med Assoc 2014;312:1055–7.CrossrefWeb of ScienceGoogle Scholar

  • 18.

    O’Gorman CS, Higgins MF, O’Neill MB. Systematic review and metaanalysis of statins for heterozygous familial hypercholesterolemia in children: evaluation of cholesterol changes and side effects. Pediatr Cardiol 2009;30:482–9.CrossrefWeb of SciencePubMedGoogle Scholar

  • 19.

    van der Graaf A, Cuffie-Jackson C, Vissers MN, Trip MD, Gagné C, et al. Efficacy and safety of coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia. J Am Coll Cardiol 2008;52:1421–9.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 20.

    Yeste D, Chacon P, Clemente M, Albisu MA, Gussinye M, et al. Ezetimibe as monotherapy in the treatment of hypercholesterolemia in children and adolescents. J Pediatr Endocrinol Metab 2009;22:487–92.PubMedGoogle Scholar

  • 21.

    Clauss S, Wai KM, Kavey RE, Kuehl K. Ezetimibe treatment of pediatric patients with hypercholesterolemia. J Pediatr 2009;154:869–72.CrossrefPubMedGoogle Scholar

  • 22.

    Araujo MB, Botto PM, Mazza CS. Use of ezetimibe in the treatment of familial hypercholesterolemia in children and adolescents. AnPediatr (Barc) 2012;77:37–42.Google Scholar

  • 23.

    Kusters DM, Caceres M, Coll M, Cuffie C, Gagné C, et al. Efficacy and safety of ezetimibe monotherapy in children with heterozygous familial or nonfamilial hypercholesterolemia. J Pediatr 2015;166:1377–84.PubMedCrossrefGoogle Scholar

  • 24.

    Ballantyne CM, Houri J, Notarbartolo A, Melani L, Lipka LJ, et al. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation 2003;107:2409–15.PubMedCrossrefGoogle Scholar

  • 25.

    Ladeiras-Lopes R, Agewall S, Tawakol A, Staels B, Stein E, et al. Atherosclerosis: recent trials, new targets and future directions. Int J Cardiol 2015;192:72–81.Web of SciencePubMedCrossrefGoogle Scholar

  • 26.

    Tyroler HA. Cholesterol and cardiovascular disease. An overview of Lipid Research Clinics (LRC) epidemiologic studies as background for the LRC Coronary Primary Prevention Trial. Am J Cardiol 1984;54:14C–19C.Google Scholar

  • 27.

    Magnussen CG, Venn A, Thomson R, Juonala M, Srinivasan SR, et al. The association of pediatric low- and high-density lipoprotein cholesterol dyslipidemia classifications and change in dyslipidemia status with carotid intima-media thickness in adulthood evidence from the cardiovascular risk in Young Finns study, the Bogalusa Heart study, and the CDAH (Childhood Determinants of Adult Health) study. J Am Coll Cardiol 2009;53:860–9.Web of ScienceGoogle Scholar

  • 28.

    Kologlu T, Ucar SK, Levent E, Akcay YD, Coker M, et al. Chitotriosidase as a possible marker of clinically evidenced atherosclerosis in dyslipidemic children. J Pediatr Endocrinol Metab 2014;27:701–8.Web of SciencePubMedGoogle Scholar

  • 29.

    Davignon J. Beneficial cardiovascular pleiotropic effects of statins. Circulation 2004;109(23 Suppl 1):III39–43.PubMedGoogle Scholar

  • 30.

    Kavalipati N, Shah J, Ramakrishan A, Vasnawala H. Pleiotropic effects ofstatins. Indian J Endocrinol Metab 2015;19:554–62.CrossrefGoogle Scholar

  • 31.

    Satoh M, Takahashi Y, Tabuchi T, Minami Y, Tamada M, et al. Cellular and molecular mechanisms of statins: an update onpleiotropic effects. Clin Sci (Lond) 2015;129:93–105.PubMedCrossrefGoogle Scholar

About the article

Received: 2016-04-01

Accepted: 2016-09-05

Published Online: 2016-10-08

Published in Print: 2016-11-01


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 29, Issue 11, Pages 1285–1291, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2016-0117.

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