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Pharmacotherapy of Hyperlipidemia in Pediatric Heart Transplant Recipients

Current Practice and Future Directions


Lipoprotein abnormalities are fairly common after pediatric heart transplantation. Graft coronary artery disease (GCAD) limits long-term survival and has been linked to elevated serum triglyceride levels and decreased high-density lipoprotein levels. Histologically, GCAD represents intimal hyperplasia of the coronary vessel and is best imaged by intravascular ultrasound.

A number of pharmacologic agents are available for the management of lipid disorders but experience with these drugs has mainly been in adults. HMG-CoA reductase inhibitors (statins) are currently used by many adult transplantation centers to alter lipid profiles in the hope of reducing GCAD. The use of statins among pediatric heart transplant centers is more limited. Although rhabdomyolysis is a concern with these agents, the incidence among individuals receiving immunosuppressant therapy is low. Aside from their lipid-lowering properties, statins may also protect against graft failure and rejection.

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  1. 1.

    Valantine HA. Role of lipids in allograft vascular disease: a multicenter study of intimai thickening detected by intravascular ultrasound. J Heart Lung Transplant 1995; 14 (6 Pt 2): S234–7

  2. 2.

    Costanzo MR, Naftel DC, Pritzker MR, et al. Heart transplant coronary artery disease detected by coronary angiography: a multi-institutional study of preoperative donor and recipient risk factors. J Heart Lung Transplant 1998; 17(8): 744–53

  3. 3.

    Gao SZ, Alderman L, Schroeder JS, et al. Accelerated coronary vascular disease in the heart transplant patient: coronary arteriographic findings. J Am Coll Cardiol 1988; 12(2): 334–40

  4. 4.

    Rickenbacher PR, Kemna MS, Pinto FJ, et al. Coronary artery intimal thickening in the transplanted heart: an in vivo intracoronary ultrasound study of immunologic and metabolic risk factors. Transplantation 1995; 61(1): 46–53

  5. 5.

    Hertz MI, Taylor DO, Trulock BP, et al. The Registry of the International Society for Heart and Lung Transplantation: nineteenth official report: 2002. J Heart Lung Transplant 2002; 21(9): 950–70

  6. 6.

    Akhlaghi F, Jackson CH, Parameshwar J, et al. Risk factors for the development and progression of dyslipidemia after heart transplantation. Transplantation 2002; 73(8): 1258–64

  7. 7.

    Chin C, Rosenthal D, Bernstein D. Lipoprotein abnormalities are highly prevalent in pediatric heart transplant recipients. Pediatr Transplant 2000; 4(3): 193–9

  8. 8.

    Keogh A, Day R, Critchely L, et al. The effect of food and cholestyramine on the absorption of cyclosporine in cardiac transplant recipients. Transplant Proc 1988; 20(1): 27–30

  9. 9.

    Pflugfelder PW, Huff M, Oskalns R, et al. Cholesterol-lowering therapy after heart transplantation: a 12-month randomized trial. J Heart Lung Transplant 1996; 14(4): 613–22

  10. 10.

    Ballantyne CM, Radovancevic B, Farmer JA, et al. Hyperlipidemia after heart transplantation: report of a 6-year experience, with treatment recommendations. J Am Coll Cardiol 1992; 19(6): 1315–21

  11. 11.

    Stapleton DD, Mehra MR, Dumas D, et al. Lipid-lowering therapy and long-term survival in heart transplantation. Am J Cardiol 1997; 80(6): 802–5

  12. 12.

    Buyukcelik M, Anarat A, Bayazit AK, et al. The effects of gemfibrozil on hyperlipidemia in children with persistent nephrotic syndrome. Turk J Pediatr 2002; 44(1): 40–4

  13. 13.

    Oberman HY, Hurst DC, Segrest JP. Niacin revisited: clinical observations on an important but underutilized drug. Am J Med 1991; 91(6): 239–46

  14. 14.

    Chin C, Gamberg P, Miller J, et al. Efficacy and safety of atorvastatin after pediatric heart transplantation. J Heart Lung Transplant 2002; 21(11): 1213–7

  15. 15.

    Penson MG, Fricker FJ, Thompson JR, et al. Safety and efficacy of pravastatin therapy for the prevention of hyperlipidemia in pediatric and adolescent cardiac transplant recipients. J Heart Lung Transplant 2001; 20(6): 611–8

  16. 16.

    Wolters Kluwer Health. Ezetimibe: facts and comparisons [online]. Available from URL: [Accessed 2005 Oct]

  17. 17.

    Gagne C, Gaudet D, Bruckert E. Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Circulation 2002; 105: 2469–75

  18. 18.

    Dujovne CA, Ettinger MP, McNeer JF, et al. Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia. Am J Cardiol 2002; 90(10): 1092–7

  19. 19.

    Billingham ME. Cardiac transplant atherosclerosis. Transplant Proc 1987; 19 (4 Suppl. 5): 19–25

  20. 20.

    Cramer DV, Chapman FA, Wu GD, et al. Cardiac transplantation in the rat: II. Alteration of the severity of donor graft arteriosclerosis by modulation of the host immune response. Transplantation 1990; 50(4): 554–8

  21. 21.

    Shi C, Lee WS, Russell ME, et al. Hypercholesterolemia exacerbates transplant arteriosclerosis via increased neointimal smooth muscle accumulation: studies in apolipoprotein E knockout mice. Circulation 1997; 96(8): 2722–8

  22. 22.

    Perrault LP, Mahlberg F, Breugnot C, et al. Hypercholesterolemia increases coronary endothelial dysfunction, lipid content, and accelerated atherosclerosis after heart transplantation. Arterioscler Thromb Vasc Biol 2000; 20(3): 728–36

  23. 23.

    Meiser BM, Wenke K, Theiry J, et al. Simvastatin decreased accelerated graft vessel disease after heart transplantation in an animal model. Transplant Proc 1993; 25(2): 2077–9

  24. 24.

    Maggard MA, Ke B, Wang T, et al. Effects of pravastatin on chronic rejection of rat cardiac allografts. Transplantation 1998; 65(2): 149–55

  25. 25.

    Sparrow CP, Burton CA, Hernandez M, et al. Simvastatin has anti-inflammatory and antiatherosclerotic activities independent of plasma cholesterol lowering. Arterioscler Thromb Vasc Biol 2001; 21(1): 115–21

  26. 26.

    Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med 1999; 340: 115–26

  27. 27.

    Ballantyne CM, Jones PH, Payton-Ross C, et al. Hyperlipidemia following heart transplantation: natural history and intervention with mevinolin (lovastatin). Transplant Proc 1987; 19 (4 Suppl. 5): 60–2

  28. 28.

    Keogh A, Macdonald P, Harrison A, et al. Hyperlipidemia after heart transplantation. J Heart Transplant 1988; 7(3): 171–5

  29. 29.

    Park JW, Merz M, Braun P, et al. Lipid disorder and transplant coronary artery disease in long-term survivors of heart transplantation. J Heart Lung Transplant 1996; 15(16): 572–9

  30. 30.

    Johnson MR. Transplant coronary disease: nonimmunologic risk factors. J Heart Lung Transplant 1992; 11 (3 Pt 2): S124–32

  31. 31.

    Kobashigawa JA, Katznelson S, Laks H, et al. Effect of pravastatin on outcomes after cardiac transplantation. N Engl J Med 1995; 333(10): 621–7

  32. 32.

    Wenke K, Meiser B, Thiery J, et al. Simvastatin reduces graft vessel disease and mortality after heart transplantation. Circulation 1997; 96(5): 1398–402

  33. 33.

    Kato T, Tokoro T, Namii Y, et al. Early introduction of HMG-CoA reductase inhibitors could prevent the incidence of transplant coronary artery disease. Transplant Proc 2000; 32(2): 331–3

  34. 34.

    Pahl E, Crawford SE, Wax DF, et al. Safety and efficacy of pravastatin in pediatric heart transplant recipients [abstract]. J Heart Lung Transplant 2001; 20(2): 230

  35. 35.

    Boucek MM, Edwards LB, Keck BM, et al. The Registry of the International Society for Heart and Lung Transplantation: fifth official pediatric report: 2001 to 2002. J Heart Lung Transplant 2002; 21(8): 827–40

  36. 36.

    Pahl E, Zales VR, Fricker FJ, et al. Post-transplant coronary artery disease in children: a multicenter national survey. Circulation 1994; 90 (5 Pt 2): 56–60

  37. 37.

    Sigfusson G, Fricker FJ, Bernstein D, et al. Long-term survivors of pediatric heart transplantation: a multicenter report of sixty-eight children who have survived longer than five years. J Pediatr 1997; 130(16): 862–71

  38. 38.

    Dent CL, Canter CE, Hirsch R, et al. Transplant coronary artery disease in pediatric heart transplant recipients. J Heart Lung Transplant 2000; 19(3): 240–8

  39. 39.

    St Goar FG, Pinto FJ, Alderman EL, et al. Intracoronary ultrasound in cardiac transplant recipients: in vivo evidence of ‘angiographically silent’ intima thickening. Circulation 1992; 85(3): 979–87

  40. 40.

    Yeung AC, Davis SF, Hauptman PJ, et al. Incidence and progression of transplant coronary artery disease over 1 year: results of a multicenter trial with use of intravascular ultrasound. J Heart Lung Transplant 1995; 14 (6 Pt 2): S215–20

  41. 41.

    Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature 1990; 343: 425–30

  42. 42.

    Cutts JL, Bankhurst AD. Suppression of lymphoid cell function in vitro by inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by lovastatin. Int J Immunopharmacol 1989; 11: 863–9

  43. 43.

    Chakrabarti R, Engleman EG. Interrelationships between mevalonate metabolism and the mitogeni signaling pathway in T lymphocyte proliferation. J Biol Chem 1991; 266: 12216–22

  44. 44.

    Kurakata S, Kada M, Shimada Y, et al. Effects of different inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, pravastatin sodium and simvastatin, on sterol synthesis and immunological functions in human lymphocytes in vitro. Immunopharmacology 1996; 34(1): 51–61

  45. 45.

    Katznelson S, Wang XM, Chia D, et al. The inhibitory effects of pravastatin on natural killer cell activity in vivo and on cytotoxic T lymphocyte activity in vitro. J Heart Lung Transplant 1998; 17(4): 335–40

  46. 46.

    Cutts JL, Bankhurst AD. Reversal of lovastatin-mediated inhibition of natural killer cell cytotoxicity by interleukin-2. J Cell Physiol 1990; 145: 244–52

  47. 47.

    Kwak B, Mulhaupt F, Myit S, et al. Statins as a newly recognized type of immunomodulator. Nat Med 2000; 6(12): 1399–402

  48. 48.

    Rudich SM, Mongini PK, Perez RV, et al. HMG-CoA reductase inhibitors pravastatin and simvastatin inhibit human B-lymphocyte activation. Transplant Proc 1998; 30(4): 992–5

  49. 49.

    Kakkis JL, Ke B, Dawson S, et al. Pravastatin increases survival and inhibits natural killer cell enhancement factor in liver transplanted rats. J Surg Res 1997; 69(2): 393–8

  50. 50.

    See Jr VY, DeNofrio D, Goldberg L, et al. Effect of atorvastatin on postcardiac transplant increase in low-density lipoprotein cholesterol reduces development of intimal hyperplasia and progression of endothial dysfunction. Am J Cardiol 2003; 92(1): 11–5

  51. 51.

    Hognestad A, Endresen K, Wergeland R, et al. Plasma C-reactive protein as a marker of cardiac allograft vasculopathy in heart transplant recipients. J Am Coll Cardiol 2003; 42(3): 477–82

  52. 52.

    Pethig K, Heublein B, Kutschka I, et al. Systemic inflammatory response in cardiac allograft vasculopathy: high-sensitive C-reactive protein is associated with progressive luminal obstruction. Circulation 2000; 102 (19 Suppl. 3): 233–6

  53. 53.

    Eisenberg MS, Chen HJ, Warshofsky MK, et al. Elevated levels of plasma C-reactive protein are associated with decreased graft survival in cardiac transplant recipients. Circulation 2000; 102(17): 2100–4

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No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Correspondence to Dr Clifford Chin.

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Chin, C., Bernstein, D. Pharmacotherapy of Hyperlipidemia in Pediatric Heart Transplant Recipients. Pediatr-Drugs 7, 391–396 (2005).

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  • Simvastatin
  • Pravastatin
  • Fenofibrate
  • Ezetimibe
  • Mycophenolate Mofetil