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Drug Therapy for Hypercholesterolemia and Dyslipidemia

  • Sarah D. de Ferranti
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The initial and primary treatment of abnormal lipid levels (Table 13-1) in children is to change diet and activity levels. Pharmacological treatment of lipid disorders is used according to guidelines published in 1992 (Table 13-2). 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; a similar approach is being taken in pediatrics (Table 13-3). New pediatric lipid guidelines are being developed and will likely reflect this type of thinking. Although atherosclerosis is known to begin in childhood, extensive outcome data are lacking in pediatrics, and parental and/or patient preferences are usually included in the decisionmaking process.

Keywords

Familial Hypercholesterolemia Bile Acid Sequestrant Lipid Research Clinic Liver Function Test Elevation Cholesterol Absorption Inhibitor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    American Academy of Pediatrics. Committee on Nutrition. Cholesterol in childhood. Pediatrics 1998; 101:141–147.Google Scholar
  2. 2.
    Obarzanek E, Kimm SY, Barton BA, Van Horn LL, Kwiterovich PO, Jr., 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; 107:256–264.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; 81:976–982.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; 251:365–374.Google Scholar
  5. 5.
    McCrindle BW, O’Neil 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;130:266–273.PubMedCrossRefGoogle Scholar
  6. 6.
    Tonstad S, Siversten M, Aksenes L, Ose L. Low dose colestipol in adolescents with familial hypercholesterolaemia. Arch Dis Child 1996;74:157–160.PubMedCrossRefGoogle 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; 51:715–721.PubMedGoogle 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; 151:273–281.PubMedCrossRefGoogle Scholar
  9. 9.
    Crouse JR, III, Furberg CD. Treatment of dyslipidemia: room for improvement? Arterioscler Thromb Vasc Biol 2000; 20:2333–2335.PubMedGoogle 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; 26:1388–1399.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; 106:2231–2237.PubMedCrossRefGoogle Scholar
  13. 13.
    Stein EA, Illingworth DR, Kwiterovich PO, Jr., 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; 281:137–144.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; 97:619–628.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; 292:331–337.PubMedCrossRefGoogle Scholar
  16. 16.
    Knipscheer HC, Boelen CC, Kastelein JJ, van Diermen DE, Groenemeijer BE, van den EA et al. Short-term efficacy and safety of pravastatin in 72 children with familial hypercholesterolemia. Pediatr Res 1996; 39:867–871.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; 150:421–428.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 RO, III, 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; 31:684–691.PubMedCrossRefGoogle Scholar
  21. 21.
    Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 11th ed. New York: McGraw-Hill; 2006.Google Scholar
  22. 22.
    Sondike SB, Cooperman N, Jacobson MS. Effects of a low-carbohydrate diet on weight loss and cardiovascular risk factor in overweight adolescents. J Pediatr 2003;142:253–258.PubMedCrossRefGoogle Scholar
  23. 23.
    O’Driscoll G, Green D, Taylor RR. Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 month. Circulation 1997; 95:1126–1131.PubMedGoogle Scholar
  24. 24.
    Laufs U, La FV, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 1998; 97:1129–1135.PubMedGoogle Scholar
  25. 25.
    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
  26. 26.
    Sleijfer S, van der GA, Planting AS, Stoter G, Verweij J. The potential of statins as part of anti-cancer treatment. Eur J Cancer 2005; 41:516–522.PubMedCrossRefGoogle Scholar
  27. 27.
    Klein BE, Klein R, Lee KE, Grady LM. Statin use and incident nuclear cataract. JAMA 2006; 295:2752–2758.PubMedCrossRefGoogle Scholar
  28. 28.
    Kajinami K, Okabayashi M, Sato R, Polisecki E, Schaefer EJ. Statin pharmacogenomics: what have we learned, and what remains unanswered? Curr Opin Lipidol 2005; 16:606–613.PubMedCrossRefGoogle Scholar
  29. 29.
    Bellosta S, Paoletti R, Corsini A. Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation 2004; 109:III50–III57.PubMedCrossRefGoogle Scholar
  30. 30.
    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; 33:976–982.PubMedCrossRefGoogle Scholar
  31. 31.
    Comparative efficacy and safety of pravastatin and cholestyramine alone and combined in patients with hypercholesterolemia. Pravastatin Multicenter Study Group II. Arch Intern Med 1993; 153:1321–1329.Google Scholar
  32. 32.
    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; 80:587–595.PubMedCrossRefGoogle Scholar
  33. 33.
    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; 97:61–67.PubMedCrossRefGoogle Scholar
  34. 34.
    Pasternak RC, Smith SC, Jr., Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C. ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins. Stroke 2002; 33:2337–2341.PubMedCrossRefGoogle Scholar
  35. 35.
    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; 292:2585–2590.PubMedCrossRefGoogle Scholar
  36. 36.
    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; 106:1943–1948.PubMedCrossRefGoogle Scholar
  37. 37.
    Altmann SW, Davis HR, Jr., Zhu LJ, Yao X, Hoos LM, Tetzloff G et al. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science 2004; 303:1201–1204.PubMedCrossRefGoogle Scholar
  38. 38.
    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; 90:1084–1091.PubMedCrossRefGoogle Scholar
  39. 39.
    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; 57:363–368.PubMedGoogle Scholar
  40. 40.
    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; 90:1092–1097.PubMedCrossRefGoogle Scholar
  41. 41.
    Watts GF, Dimmitt SB. Fibrates, dyslipoproteinaemia and cardiovascular disease. Curr Opin Lipidol 1999; 10:561–574.PubMedCrossRefGoogle Scholar
  42. 42.
    Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation 1998; 98:2088–2093.PubMedGoogle Scholar
  43. 43.
    Büyükc¸elik M, Anarat A, Bayazit AK, Noyan A, Ozel A, Anarat R, et al. The effects of gemfibrozil on hyperlipidemia in children with persistent nephritic syndrome. Turk J Pediatr 2002;44:40–44.Google Scholar
  44. 44.
    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; 45:1835–1845.PubMedCrossRefGoogle Scholar
  45. 45.
    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; 17:2020–2028.PubMedGoogle Scholar
  46. 46.
    Carlson LA. Nicotinic acid: the broad-spectrum lipid drug. A 50th anniversary review. J Intern Med 2005; 258:94–114.PubMedCrossRefGoogle Scholar
  47. 47.
    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; 34:642–650.PubMedCrossRefGoogle Scholar
  48. 48.
    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
  49. 49.
    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
  50. 50.
    Iwaki M, Ogiso T, Hayashi H, Tanino T, Benet LZ. Acute dose-dependent disposition studies of nicotinic acid in rats. Drug Metab Dispos 1996; 24:773–779.PubMedGoogle Scholar
  51. 51.
    Henkin Y, Oberman A, Hurst DC, Segrest JP. Niacin revisited: clinical observations on an important but underutilized drug. Am J Med 1991; 91:239–246.PubMedCrossRefGoogle Scholar
  52. 52.
    Marchioli R, Barzi F, Bomba E, Chieffo C, Di Gregorio D, Di Mascio R, et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione. Circulation 2002;105:1897–1903.PubMedCrossRefGoogle Scholar
  53. 53.
    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; 42:672–679.PubMedGoogle Scholar
  54. 54.
    American Academy of Pediatrics Committee on Nutrition: Statement on cholesterol. Pediatrics 1992; 90:469–473.Google Scholar

Copyright information

© Springer-Verlag London Limited 2008

Authors and Affiliations

  • Sarah D. de Ferranti
    • 1
  1. 1.Department of CardiologyChildren's Hospital BostonBostonUSA

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