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New directions in immunosuppression after heart transplantation

Nature Reviews Cardiology volume 10, pages 422–427 (2013)Cite this article

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Abstract

Heart transplantation has evolved into the treatment of choice for eligible patients with end-stage heart failure. Effective immunosuppression is critical to the success of this treatment, with the modern era beginning with the advent of cyclosporin A in the 1980s. In this Perspectives article, the major prospective, randomized trials of immunosuppression after heart transplantation are briefly reviewed. These trials provided the setting for the 2011 TICTAC trial, in which combined immunosuppression was compared with monotherapy. The results of the study are discussed, as are the implications of these data for future research, including the importance of frameworks, the risks and benefits of changes in immunosuppression regimen, the future of funding for such research, and the selection of appropriate end points in trials of heart transplantation. The presupposed need for multidrug immunosuppression is challenged, and the potential efficacy and benefits of monotherapy are explored.

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Figure 1: Kaplan–Meier plots of survival after heart transplantation.

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References

  1. Barnard, C. N. The operation. A human cardiac transplant: an interim report of a successful operation performed at Groote Schuur Hospital, Cape Town. S. Afr. Med. J. 41, 1271–1274 (1967).

    CAS  PubMed  Google Scholar 

  2. Lawrence, S. V. Heart transplants: blessing or boondoggle? Forum Med. 3, 441–445 (1980).

    CAS  PubMed  Google Scholar 

  3. Caves, P. K. et al. Percutaneous transvenous endomyocardial biopsy. JAMA 225, 288–291 (1973).

    Article  CAS  Google Scholar 

  4. Ridker, A. K. et al. The status of cardiac transplantation, 1975. Circulation 52, 531–539 (1975).

    Article  Google Scholar 

  5. Leaf, A. Sounding board: the MGH trustees say no to heart transplants. N. Engl. J. Med. 302, 1087–1088 (1980).

    Article  CAS  Google Scholar 

  6. Halloran, P. F., Lien, J., Aprile, M. & White, N. Preliminary results of a randomized comparison of cyclosporine and Minnesota Antilymphoblast Globulin. Transplant. Proc. 14, 627–630 (1982).

    CAS  PubMed  Google Scholar 

  7. Devineni, R. et al. Cyclosporine in cardiac transplantation. Can. J. Surg. 27, 252–254 (1984).

    CAS  PubMed  Google Scholar 

  8. Stehlik, J. et al. The registry of the International Society for Heart and Lung Transplantation: 29th official adult heart transplant report—2012. J. Heart Lung Transplant. 31, 1052–1064 (2012).

    Article  Google Scholar 

  9. Kobashigawa, J. et al. A randomized active-controlled trial of mycophenolate mofetil in heart transplant recipients. Mycophenolate Mofetil Investigators. Transplantation 66, 507–515 (1998).

    Article  CAS  Google Scholar 

  10. Kobashigawa, J. A. et al. Mycophenolate mofetil reduces intimal thickness by intravascular ultrasound after heart transplant: reanalysis of the multicenter trial. Am. J. Transplant. 6, 993–997 (2006).

    Article  CAS  Google Scholar 

  11. Eisen, H. J. et al. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N. Engl. J. Med. 349, 847–858 (2003).

    Article  CAS  Google Scholar 

  12. Kobashigawa, J. A. et al. Multicenter intravascular ultrasound validation study among heart transplant recipients: outcomes after five years. J. Am. Coll. Cardiol. 45, 1532–1537 (2005).

    Article  Google Scholar 

  13. Kobashigawa, J. A. et al. Tacrolimus with mycophenolate mofetil (MMF) or sirolimus vs. cyclosporine with MMF in cardiac transplant patients: 1-year report. Am. J. Transplant. 6, 1377–1386 (2006).

    Article  CAS  Google Scholar 

  14. Grimm, M. et al. Superior prevention of acute rejection by tacrolimus vs. cyclosporine in heart transplant recipients—a large European trial. Am. J. Transplant. 6, 1387–1397 (2006).

    Article  CAS  Google Scholar 

  15. Baran, D. A. Induction therapy in cardiac transplantation: when and why? Heart Fail. Clin. 3, 31–41 (2007).

    Article  Google Scholar 

  16. Uber, P. A. & Mehra, M. R. Induction therapy in heart transplantation: is there a role? J. Heart Lung Transplant. 26, 205–209 (2007).

    Article  Google Scholar 

  17. Hershberger, R. E. et al. Daclizumab to prevent rejection after cardiac transplantation. N. Engl. J. Med. 352, 2705–2713 (2005).

    Article  CAS  Google Scholar 

  18. Baran, D. A. et al. Tacrolimus in cardiac transplantation: efficacy and safety of a novel dosing protocol. Transplantation 74, 1136–1141 (2002).

    Article  CAS  Google Scholar 

  19. Baran, D. A. et al. Tacrolimus monotherapy inadult cardiac transplant recipients: intermediate-term results. J. Heart Lung Transplant. 20, 59–70 (2001).

    Article  CAS  Google Scholar 

  20. Lubitz, S. A. et al. Long-term results of tacrolimus monotherapy in cardiac transplant recipients. J. Heart Lung Transplant. 25, 699–706 (2006).

    Article  Google Scholar 

  21. Baran, D. A. et al. Randomized trial of tacrolimus monotherapy: tacrolimus in combination, tacrolimus alone compared (the TICTAC trial). J. Heart Lung Transplant. 26, 992–997 (2007).

    Article  Google Scholar 

  22. Mehra, M. R. et al. An intravascular ultrasound study of the influence of angiotensin-converting enzyme inhibitors and calcium entry blockers on the development of cardiac allograft vasculopathy. Am. J. Cardiol. 75, 853–854 (1995).

    Article  CAS  Google Scholar 

  23. Yamani, M. H. et al. Does acute cellular rejection correlate with cardiac allograft vasculopathy? J. Heart Lung Transplant. 23, 272–276 (2004).

    Article  Google Scholar 

  24. Baran, D. A. et al. A prospective, randomized trial of single-drug versus dual-drug immunosuppression in heart transplantation: the tacrolimus in combination, tacrolimus alone compared (TICTAC) trial. Circ. Heart Fail. 4, 129–137 (2011).

    Article  CAS  Google Scholar 

  25. Dresske, B. et al. WOFIE stimulates regulatory T cells: a 2-year follow-up of renal transplant recipients. Transplantation 81, 1549–1557 (2006).

    Article  Google Scholar 

  26. Calne, R. Y. et al. Tolerance of porcine renal allografts induced by donor spleen cells and seven days' treatment with cyclosporine. Transplantation 57, 1433–1435 (1994).

    Article  CAS  Google Scholar 

  27. Urschel, S. et al. ABO-incompatible heart transplantation in early childhood: an international multicenter study of clinical experiences and limits. J. Heart Lung Transplant. 32, 285–292 (2013).

    Article  Google Scholar 

  28. Becker, T. et al. Patient outcomes in two steroid-free regimens using tacrolimus monotherapy after daclizumab induction and tacrolimus with mycophenolate mofetil in liver transplantation. Transplantation 86, 1689–1694 (2008).

    Article  CAS  Google Scholar 

  29. Schneeberger, S. et al. Upper-extremity transplantation using a cell-based protocol to minimize immunosuppression. Ann. Surg. 257, 345–351 (2013).

    Article  Google Scholar 

  30. US Department of Health & Human Sciences: FDA. Important drug information [online], (2009).

  31. Clinical Trials in Organ Transplantation. Approved studies [online], (2013).

  32. Shah, M. R., Starling, R. C., Schwartz Longacre, L. & Mehra, M. R. Heart transplantation research in the next decade—a goal to achieving evidence-based outcomes: National Heart, Lung, and Blood Institute Working Group. J. Am. Coll. Cardiol. 59, 1263–1269 (2012).

    Article  Google Scholar 

  33. Eisen, H. J. et al. Three-year results of a randomized, double-blind, controlled trial of mycophenolate mofetil versus azathioprine in cardiac transplant recipients. J. Heart Lung Transplant. 24, 517–525 (2005).

    Article  Google Scholar 

  34. Kobashigawa, J. et al. Daclizumab is associated with decreased rejection and no increased mortality in cardiac transplant patients receiving MMF, cyclosporine, and corticosteroids. Transplant. Proc. 37, 1333–1339 (2005).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Newark Beth Israel Medical Center, 201 Lyons Avenue, L-4, Transplant Center, Newark, 07112, NJ, USA

    David A. Baran

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  1. David A. Baran
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The author has received grant or research support from Astellas Pharmaceuticals.

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Baran, D. New directions in immunosuppression after heart transplantation. Nat Rev Cardiol 10, 422–427 (2013). https://doi.org/10.1038/nrcardio.2013.63

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