Skip to main content
SpringerLink
Log in

Drug Therapy for Hypercholesterolemia and Dyslipidemia

  • Chapter
  • First Online:
Handbook of Pediatric Cardiovascular Drugs

  • 1802 Accesses

Abstract

The initial and primary treatment of abnormal lipid levels in children is to change diet and activity levels. Pharmacological treatment of lipid disorders is used according to guidelines published in 2011. In adults treatment cutpoints and goals for therapy are adjusted based on high risk populations and in the presence of other cardiovascular (CV) risk factors. Pediatric lipid guidelines also reflect this type of thinking, although the data on which treatment cutpoints are based is less robust than adults. Atherosclerosis is known to begin in childhood; however, extensive outcome data are lacking in pediatrics and parental and/or patient preference are usually included in the decision-making process.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. American Academy of Pediatrics. Committee on Nutrition. Cholesterol in childhood. Pediatrics 1998;101:141–7.

    Google Scholar 

  2. Obarzanek E, Kimm SY, Barton BA, Van Horn LL, Kwiterovich Jr PO, Simons-Morton DG, et al. Long-term safety and efficacy of a cholesterol-lowering diet in children with elevated low-density lipoprotein cholesterol: seven-year results of the Dietary Intervention Study in Children (DISC). Pediatrics. 2001;107:256–64.

    Article  CAS  PubMed  Google Scholar 

  3. Ebbeling CB, Leidig MM, Sinclair KB, Seger-Shippee LG, Feldman HA, Ludwig DS. Effects of an ad libitum low-glycemic load diet on cardiovascular disease risk factors in obese young adults. Am J Clin Nutr. 2005;81:976–82.

    CAS  PubMed  Google Scholar 

  4. The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA. 1984;251:365–74.

    Google Scholar 

  5. McCrindle BW, O’Neill MB, Cullen-Dean G, Helden E. Acceptability and compliance with two forms of cholestyramine in the treatment of hypercholesterolemia in children: a randomized, crossover trial. J Pediatr. 1997;130(2):266–73.

    Google Scholar 

  6. Tonstad S, Knudtzon J, Sivertsen M, Refsum H, Ose L. Efficacy and safety of cholestyramine therapy in peripubertal and prepubertal children with familial hypercholesterolemia. J Pediatr. 1996;129(1):42–9.

    Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. Zhou Z, Rahme E, Pilote L. Are statins created equal? Evidence from randomized trials of pravastatin, simvastatin, and atorvastatin for cardiovascular disease prevention. Am Heart J. 2006;151:273–81.

    Article  CAS  PubMed  Google Scholar 

  9. Crouse III JR, Furberg CD. Treatment of dyslipidemia: room for improvement? Arterioscler Thromb Vasc Biol. 2000;20:2333–5.

    Article  PubMed  Google Scholar 

  10. Jones PH, Hunninghake DB, Ferdinand KC, Stein EA, Gold A, Caplan RJ, et al. Effects of rosuvastatin versus atorvastatin, simvastatin, and pravastatin on non-high-density lipoprotein cholesterol, apolipoproteins, and lipid ratios in patients with hypercholesterolemia: additional results from the STELLAR trial. Clin Ther. 2004;26:1388–99.

    Article  CAS  PubMed  Google Scholar 

  11. Ducobu J, Brasseur D, Chaudron JM, Deslypere JP, Harvengt C, Muls E, et al. Simvastatin use in children. Lancet. 1992;339:1488.

    Article  CAS  PubMed  Google Scholar 

  12. de Jongh S, Ose L, Szamosi T, Gagne C, Lambert M, Scott R, et al. Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized, double-blind, placebo-controlled trial with simvastatin. Circulation. 2002;106:2231–7.

    Article  PubMed  Google Scholar 

  13. Stein EA, Illingworth DR, Kwiterovich Jr PO, Liacouras CA, Siimes MA, Jacobson MS, et al. Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia: a randomized controlled trial. JAMA. 1999;281:137–44.

    Article  CAS  PubMed  Google Scholar 

  14. Lambert M, Lupien PJ, Gagne C, Levy E, Blaichman S, Langlois 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.

    CAS  PubMed  Google Scholar 

  15. Wiegman A, Hutten BA, de Groot E, Rodenburg J, Bakker HD, Buller HR, et al. Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized controlled trial. JAMA. 2004;292:331–7.

    Article  CAS  PubMed  Google Scholar 

  16. Knipscheer HC, Boelen CC, Kastelein JJ, van Diermen DE, Groenemeijer BE, van den Ende A, et al. Short-term efficacy and safety of pravastatin in 72 children with familial hypercholesterolemia. Pediatr Res. 1996;39:867–71.

    Article  CAS  PubMed  Google Scholar 

  17. Raal FJ, Pappu AS, Illingworth DR, Pilcher GJ, Marais AD, Firth JC, et al. Inhibition of cholesterol synthesis by atorvastatin in homozygous familial hypercholesterolaemia. Atherosclerosis. 2000;150:421–8.

    Article  CAS  PubMed  Google Scholar 

  18. McCrindle BW, Ose L, Marais AD. Efficacy and safety of atorvastatin in children and adolescents with familial hypercholesterolemia or severe hyperlipidemia: a multicenter, randomized, placebo-controlled trial. J Pediatr. 2003;143:74–80.

    Article  CAS  PubMed  Google Scholar 

  19. Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon III RO, Criqui M, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003;107:499–511.

    Article  PubMed  Google Scholar 

  20. Williams JK, Sukhova GK, Herrington DM, Libby P. Pravastatin has cholesterol-lowering independent effects on the artery wall of atherosclerotic monkeys. J Am Coll Cardiol. 1998;31:684–91.

    Article  CAS  PubMed  Google Scholar 

  21. O’Driscoll G, Green D, Taylor RR. Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 month. Circulation. 1997;95:1126–31.

    Article  PubMed  Google Scholar 

  22. Laufs U, La FV, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation. 1998;97:1129–35.

    Article  CAS  PubMed  Google Scholar 

  23. Aviram M, Hussein O, Rosenblat M, Schlezinger S, Hayek T, Keidar S. Interactions of platelets, macrophages, and lipoproteins in hypercholesterolemia: antiatherogenic effects of HMG-CoA reductase inhibitor therapy. J Cardiovasc Pharmacol. 1998;31:39–45.

    Article  CAS  PubMed  Google Scholar 

  24. Sleijfer S, van der Gaast A, Planting AS, Stoter G, Verweij J. The potential of statins as part of anti-cancer treatment. Eur J Cancer. 2005;41:516–22.

    Article  CAS  PubMed  Google Scholar 

  25. Klein BE, Klein R, Lee KE, Grady LM. Statin use and incident nuclear cataract. JAMA. 2006;295:2752–8.

    Article  CAS  PubMed  Google Scholar 

  26. Kajinami K, Okabayashi M, Sato R, Polisecki E, Schaefer EJ. Statin pharmacogenomics: what have we learned, and what remains unanswered? Curr Opin Lipidol. 2005;16:606–13.

    Article  CAS  PubMed  Google Scholar 

  27. Bellosta S, Paoletti R, Corsini A. Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation. 2004;109:III50–7.

    Article  PubMed  Google Scholar 

  28. Miettinen TA, Gylling H. Synthesis and absorption markers of cholesterol in serum and lipoproteins during a large dose of statin treatment. Eur J Clin Invest. 2003;33:976–82.

    Article  CAS  PubMed  Google Scholar 

  29. Comparative efficacy and safety of pravastatin and cholestyramine alone and combined in patients with hypercholesterolemia. Pravastatin Multicenter Study Group II. Arch Intern Med. 1993;153:1321–9.

    Google Scholar 

  30. Pearson TA, Denke MA, McBride PE, Battisti WP, Brady WE, Palmisano J. A community-based, randomized trial of ezetimibe added to statin therapy to attain NCEP ATP III goals for LDL cholesterol in hypercholesterolemic patients: the ezetimibe add-on to statin for effectiveness (EASE) trial. Mayo Clin Proc. 2005;80:587–95.

    Article  CAS  PubMed  Google Scholar 

  31. Newman C, Tsai J, Szarek M, Luo D, Gibson E. Comparative safety of atorvastatin 80 mg versus 10 mg derived from analysis of 49 completed trials in 14,236 patients. Am J Cardiol. 2006;97:61–7.

    Article  CAS  PubMed  Google Scholar 

  32. Pasternak RC, Smith Jr SC, Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. Stroke. 2002;33:2337–41.

    Article  PubMed  Google Scholar 

  33. Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L, et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA. 2004;292:2585–90.

    Article  CAS  PubMed  Google Scholar 

  34. Sudhop T, Lutjohann D, Kodal A, Igel M, Tribble DL, Shah S, et al. Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation. 2002;106:1943–8.

    Article  CAS  PubMed  Google Scholar 

  35. Altmann SW, Davis Jr HR, Zhu LJ, Yao X, Hoos LM, Tetzloff G, et al. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science. 2004;303:1201–4.

    Article  CAS  PubMed  Google Scholar 

  36. Gagne C, Bays HE, Weiss SR, Mata P, Quinto K, Melino M, et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am J Cardiol. 2002;90:1084–91.

    Article  CAS  PubMed  Google Scholar 

  37. Knopp RH, Dujovne CA, Le Beaut A, Lipka LJ, Suresh R, Veltri EP. Evaluation of the efficacy, safety, and tolerability of ezetimibe in primary hypercholesterolaemia: a pooled analysis from two controlled phase III clinical studies. Int J Clin Pract. 2003;57:363–8.

    CAS  PubMed  Google Scholar 

  38. Dujovne CA, Ettinger MP, McNeer JF, Lipka LJ, LeBeaut AP, Suresh R, et al. Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia. Am J Cardiol. 2002;90:1092–7.

    Article  CAS  PubMed  Google Scholar 

  39. Watts GF, Dimmitt SB. Fibrates, dyslipoproteinaemia and cardiovascular disease. Curr Opin Lipidol. 1999;10:561–74.

    Article  CAS  PubMed  Google Scholar 

  40. Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation. 1998;98:2088–93.

    Article  CAS  PubMed  Google Scholar 

  41. Ganji SH, Tavintharan S, Zhu D, Xing Y, Kamanna VS, Kashyap ML. Niacin noncompetitively inhibits DGAT2 but not DGAT1 activity in HepG2 cells. J Lipid Res. 2004;45:1835–45.

    Article  CAS  PubMed  Google Scholar 

  42. Jin FY, Kamanna VS, Kashyap ML. Niacin decreases removal of high-density lipoprotein apolipoprotein A-I but not cholesterol ester by Hep G2 cells. Implication for reverse cholesterol transport. Arterioscler Thromb Vasc Biol. 1997;17:2020–8.

    Article  CAS  PubMed  Google Scholar 

  43. Carlson LA. Nicotinic acid: the broad-spectrum lipid drug. A 50th anniversary review. J Intern Med. 2005;258:94–114.

    Article  CAS  PubMed  Google Scholar 

  44. Knopp RH, Ginsberg J, Albers JJ, Hoff C, Ogilvie JT, Warnick GR, et al. Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: clues to mechanism of action of niacin. Metabolism. 1985;34:642–50.

    Article  CAS  PubMed  Google Scholar 

  45. Vega GL, Grundy SM. Lipoprotein responses to treatment with lovastatin, gemfibrozil, and nicotinic acid in normolipidemic patients with hypoalphalipoproteinemia. Arch Intern Med. 1994;154:73–82.

    Article  CAS  PubMed  Google Scholar 

  46. Colletti RB, Neufeld EJ, Roff NK, McAuliffe TL, Baker AL, Newburger JW. Niacin treatment of hypercholesterolemia in children. Pediatrics. 1993;92:78–82.

    CAS  PubMed  Google Scholar 

  47. Iwaki M, Ogiso T, Hayashi H, Tanino T, Benet LZ. Acute dose-dependent disposition studies of nicotinic acid in rats. Drug Metab Dispos. 1996;24:773–9.

    CAS  PubMed  Google Scholar 

  48. Henkin Y, Oberman A, Hurst DC, Segrest JP. Niacin revisited: clinical observations on an important but underutilized drug. Am J Med. 1991;91:239–46.

    Article  CAS  PubMed  Google Scholar 

  49. Engler MM, Engler MB, Malloy M, Chiu E, Besio D, Paul S, et al. Docosahexaenoic acid restores endothelial function in children with hyperlipidemia: results from the EARLY study. Int J Clin Pharmacol Ther. 2004;42:672–9.

    Article  CAS  PubMed  Google Scholar 

  50. American Academy of Pediatrics Committee on Nutrition. Statement on cholesterol. Pediatrics. 1992;90:469–73.

    Google Scholar 

  51. Sondike SB, Copperman N, Jacobson MS. Effects of a low-carbohydrate diet on weight loss and cardiovascular risk factor in overweight adolescents. J Pediatr. 2003;142(3):253–8.

    Google Scholar 

  52. http://www.nhlbi.nih.gov/guidelines/cvd_ped/.

Download references

Author information

Authors and Affiliations

  1. Preventive Cardiology, Children’s Hospital Boston, Harvard Medical School, Boston, MA, USA

    Sarah D. de Ferranti MD, MPH

Authors
  1. Sarah D. de Ferranti MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sarah D. de Ferranti MD, MPH .

Editor information

Editors and Affiliations

  1. Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Ricardo Munoz

  2. Children’s Hospital Colorado, Aurora, Colorado, USA

    Eduardo M. da Cruz

  3. Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Carol G. Vetterly

  4. Cincinnati Children’s Hospital, Cincinnati, USA

    David S. Cooper

  5. Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Donald Berry

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag London

About this chapter

Cite this chapter

de Ferranti, S.D. (2014). Drug Therapy for Hypercholesterolemia and Dyslipidemia. In: Munoz, R., da Cruz, E., Vetterly, C., Cooper, D., Berry, D. (eds) Handbook of Pediatric Cardiovascular Drugs. Springer, London. https://doi.org/10.1007/978-1-4471-2464-1_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-2464-1_16

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-2463-4

  • Online ISBN: 978-1-4471-2464-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation