Drug Therapy for Hypercholesterolemia and Dyslipidemia

Chapter
First Online:

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.

Keywords

Hypercholesterolemia Dyslipidemia Bile acid sequestrants 
This is a preview of subscription content, log in to check access.

References

  1. 1.
    American Academy of Pediatrics. Committee on Nutrition. Cholesterol in childhood. Pediatrics 1998;101:141–7.Google Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. 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.PubMedGoogle Scholar
  4. 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. 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. 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. 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.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 9.
    Crouse III JR, Furberg CD. Treatment of dyslipidemia: room for improvement? Arterioscler Thromb Vasc Biol. 2000;20:2333–5.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 11.
    Ducobu J, Brasseur D, Chaudron JM, Deslypere JP, Harvengt C, Muls E, et al. Simvastatin use in children. Lancet. 1992;339:1488.PubMedCrossRefGoogle Scholar
  12. 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.PubMedCrossRefGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 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.PubMedGoogle Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 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.PubMedCrossRefGoogle Scholar
  23. 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.PubMedCrossRefGoogle Scholar
  24. 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.PubMedCrossRefGoogle Scholar
  25. 25.
    Klein BE, Klein R, Lee KE, Grady LM. Statin use and incident nuclear cataract. JAMA. 2006;295:2752–8.PubMedCrossRefGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 27.
    Bellosta S, Paoletti R, Corsini A. Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation. 2004;109:III50–7.PubMedCrossRefGoogle Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 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. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 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.PubMedCrossRefGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. 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.PubMedGoogle Scholar
  38. 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.PubMedCrossRefGoogle Scholar
  39. 39.
    Watts GF, Dimmitt SB. Fibrates, dyslipoproteinaemia and cardiovascular disease. Curr Opin Lipidol. 1999;10:561–74.PubMedCrossRefGoogle Scholar
  40. 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.PubMedCrossRefGoogle Scholar
  41. 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.PubMedCrossRefGoogle Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 43.
    Carlson LA. Nicotinic acid: the broad-spectrum lipid drug. A 50th anniversary review. J Intern Med. 2005;258:94–114.PubMedCrossRefGoogle Scholar
  44. 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.PubMedCrossRefGoogle Scholar
  45. 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.PubMedCrossRefGoogle Scholar
  46. 46.
    Colletti RB, Neufeld EJ, Roff NK, McAuliffe TL, Baker AL, Newburger JW. Niacin treatment of hypercholesterolemia in children. Pediatrics. 1993;92:78–82.PubMedGoogle Scholar
  47. 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.PubMedGoogle Scholar
  48. 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.PubMedCrossRefGoogle Scholar
  49. 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.PubMedCrossRefGoogle Scholar
  50. 50.
    American Academy of Pediatrics Committee on Nutrition. Statement on cholesterol. Pediatrics. 1992;90:469–73.Google Scholar
  51. 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. 52.

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  1. 1.Preventive CardiologyChildren’s Hospital Boston, Harvard Medical SchoolBostonUSA

Personalised recommendations