BioDrugs

, Volume 21, Issue 3, pp 139–143

Tacrolimus in Heart Transplant Recipients

An Overview
Leading Article

Abstract

The development of cyclosporine was pivotal in allowing cardiac transplantation to become an accepted treatment for patients with end-stage heart disease. More recently, tacrolimus has become available as a useful alternative to cyclosporine, and has been successfully combined with either azathioprine or the newer anti-proliferative agents, mycophenolate mofetil or sirolimus. Numerous randomized clinical trials have demonstrated that tacrolimus is comparable to cyclosporine in terms of overall patient survival and at least equally effective in preventing acute rejection. In addition, tacrolimus has been particularly effective as a rescue treatment in cases where recurrent rejection has occurred with cyclosporine.

The adverse effects of tacrolimus differ from those of cyclosporine, and the drug particularly shows an improved profile with respect to hypertension, dyslipidemia, and long-term renal function. These data have recently led to the regulatory approval of tacrolimus for primary immunosuppression in patients undergoing cardiac transplantation in the US.

References

  1. 1.
    Behr TM, Richter K, Fischer P, et al. Incidence of humoral rejection in heart transplant recipients treated with tacrolimus or cyclosporine A. Transplant Proc 1998; 30(5): 1920–1PubMedCrossRefGoogle Scholar
  2. 2.
    Jurcevic S, Dunn MJ, Crisp S, et al. A new enzyme-linked immunosorbent assay to measure anti-endothelial antibodies after cardiac transplantation demonstrates greater inhibition of antibody formation by tacrolimus compared with cyclosporine. Transplantation 1998; 65(9): 1197–202PubMedCrossRefGoogle Scholar
  3. 3.
    Taylor DO, Edwards LB, Boucek MM, et al. Registry of the International Society for Heart and Lung Transplantation: Twenty-third Official Adult Heart Transplantation Report - 2006. J Heart Lung Transplant 2006; 25(8): 869–79PubMedCrossRefGoogle Scholar
  4. 4.
    Goto T, Kino T, Hatanaka H, et al. Discovery of FK-506, a novel immunosuppressant isolated from Streptomyces tsukubaensis. Transplant Proc 1987; 19(5 Suppl. 6): 4–8PubMedGoogle Scholar
  5. 5.
    Migita K, Origuchi T, Kawabe Y, et al. FK506 markedly enhances apoptosis of antigen-stimulated peripheral T cells by down-regulation of Bcl-xL. Transplantation 1999; 68(7): 1018–23PubMedCrossRefGoogle Scholar
  6. 6.
    Kaibori M, Sakitani K, Oda M, et al. Immunosuppressant FK506 inhibits inducible nitric oxide synthase gene expression at a step of NF-κB activation in rat hepatocytes. J Hepatol 1999; 30(6): 1138–45PubMedCrossRefGoogle Scholar
  7. 7.
    Hamalainen M, Lahti A, Moilanen E. Calcineurin inhibitors, cyclosporin A and tacrolimus inhibit expression of inducible nitric oxide synthase in colon epithelial and macrophage cell lines. Eur J Pharmacol 2002; 448(2–3): 239–44PubMedCrossRefGoogle Scholar
  8. 8.
    Wang CH, Ko WJ, Chou NK, et al. Therapeutic drug monitoring of tacrolimus in cardiac transplant recipients: a comparison with cyclosporine neoral. Transplant Proc 2004; 36(8): 2386–7PubMedCrossRefGoogle Scholar
  9. 9.
    Armitage JM, Fricker FJ, Del Nido P, et al. The clinical trial of FK 506 as primary and rescue immunosuppression in pediatric cardiac transplantation. Transplant Proc 1991; 23(6): 3058–60PubMedGoogle Scholar
  10. 10.
    Pham SM, Kormos RL, Hattler BG, et al. A prospective trial of tacrolimus (FK 506) in clinical heart transplantation: intermediate-term results. J Thorac Cardiovasc Surg 1996; 111(4): 764–72PubMedCrossRefGoogle Scholar
  11. 11.
    Onsager DR, Canver CC, Jahania MS, et al. Efficacy of tacrolimus in the treatment of refractory rejection in heart and lung transplant recipients. J Heart Lung Transplant 1999; 18(5): 448–55PubMedCrossRefGoogle Scholar
  12. 12.
    Cantin B, Kwok BW, Shiba N, et al. Post-operative conversion from cyclosporine to tacrolimus in heart transplantation: a single-center experience. J Heart Lung Transplant 2003; 22(7): 723–30PubMedCrossRefGoogle Scholar
  13. 13.
    Taylor DO, Barr ML, Radovancevic B, et al. A randomized, multicenter comparison of tacrolimus and cyclosporine immunosuppressive regimens in cardiac transplantation: decreased hyperlipidemia and hypertension with tacrolimus. J Heart Lung Transplant 1999; 18(4): 336–45PubMedCrossRefGoogle Scholar
  14. 14.
    Reichart B, Meiser B, Vigano M, et al. European Multicenter Tacrolimus (FK506) Heart Pilot Study: one-year results — European Tacrolimus Multicenter Heart Study Group. J Heart Lung Transplant 1998; 17(8): 775–81PubMedGoogle Scholar
  15. 15.
    Grimm M, Rinaldi M, Yonan NA, et al. Superior prevention of acute rejection by tacrolimus vs. cyclosporine in heart transplant recipients: a large European trial. Am J Transplant 2006; 6(6): 1387–97PubMedCrossRefGoogle Scholar
  16. 16.
    Kobashigawa JA, Patel J, Furukawa H, et al. Five-year results of a randomized, single-center study of tacrolimus vs microemulsion cyclosporine in heart transplant patients. J Heart Lung Transplant 2006; 25(4): 434–9PubMedCrossRefGoogle Scholar
  17. 17.
    Cooney GF, Jeevanandam V, Choudhury S, et al. Comparative bioavailability of neoral and sandimmune in cardiac transplant recipients over 1 year. Transplant Proc 1998; 30(5): 1892–4PubMedCrossRefGoogle Scholar
  18. 18.
    Eisen HJ, Hobbs RE, Davis SF, et al. Safety, tolerability, and efficacy of cyclosporine microemulsion in heart transplant recipients: a randomized, multicenter, double-blind comparison with the oil-based formulation of cyclosporine — results at 24 months after transplantation. Transplantation 2001; 71(1): 70–8PubMedCrossRefGoogle Scholar
  19. 19.
    Garlicki M, Czub P, Labus K, et al. Conversion from cyclosporine to tacrolimus improves renal function and lipid profile after cardiac transplantation. Ann Transplant 2006; 11(1): 24–7PubMedGoogle Scholar
  20. 20.
    Keogh A, Richardson M, Ruygrok P, et al. Sirolimus in de novo heart transplant recipients reduces acute rejection and prevents coronary artery disease at 2 years: a randomized clinical trial. Circulation 2004; 110(17): 2694–700PubMedCrossRefGoogle Scholar
  21. 21.
    Eisen HJ, Tuzcu EM, Dorent R, et al. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med 2003; 349(9): 847–58PubMedCrossRefGoogle Scholar
  22. 22.
    Kobashigawa J, Miller L, Renlund D, et al. A randomized active-controlled trial of mycophenolate mofetil in heart transplant recipients. Mycophenolate Mofetil Investigators. Transplantation 1998; 66(4): 507–15PubMedCrossRefGoogle Scholar
  23. 23.
    Kobashigawa JA, Miller LW, Russell SD, et al. Tacrolimus with mycophenolate mofetil (MMF) or sirolimus vs. cyclosporine with MMF in cardiac transplant patients: 1-year report. Am J Transplant 2006; 6(6): 1377–86PubMedCrossRefGoogle Scholar
  24. 24.
    Aguero J, Almenar L, Martinez-Dolz L, et al. Variations in the frequency and type of infections in heart transplantation according to the immunosuppression regimen. Transplant Proc 2006; 38(8): 2558–9PubMedCrossRefGoogle Scholar
  25. 25.
    Lubitz SA, Baran DA, Alwarshetty MM, et al. Long-term results of tacrolimus monotherapy in cardiac transplant recipients. J Heart Lung Transplant 2006; 25(6): 699–706PubMedCrossRefGoogle Scholar
  26. 26.
    Newark Beth Israel Medical Center. Safety outcomes of lower immunosuppression vs traditional immunosuppression in heart transplant recipients [online]. Available from URL: http://www.clinicaltrials.gov/ct/show/NCT00299221?.order=1 [Accessed 2007 Apr 2]
  27. 27.
    Alloway R, Vanhaecke J, Yonan N, et al. Conversion of stable heart transplant recipients from twice daily prograf to once daily modified release tacrolimus [abstract]. Transplantation 2006; 82(1 Suppl. 3): 553Google Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  1. 1.Division of CardiologyDavid Geffen School of Medicine at UCLALos AngelesUSA

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