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At the present time, what is the best immunosuppression protocol for orthotopic heart transplantation?
Juan Prohias, MD
I believe the best current immunosuppression protocol for orthotopic heart transplantation includes cyclosporine (CsA), prednisone, and mycophenolate mofetil (MMF).
Cyclosporine has been used extensively over the past 20 years and has been demonstrated to improve survival in all solid organ transplants. Most transplant physicians are experienced with this medication and are aware of side effects and drug-drug interactions. Recently, the use of tacrolimus (TAC) has had some support, and in some programs, has replaced CsA as the mainstay of therapy. In 2 randomized trials comparing CsA to TAC, there were no significant differences in survival, rejection, and infection. However, there was less hirsutism, gingival hyperplasia, hypertension, and hyperlipidemia in the TAC group.
We have recently completed our own randomized trial of the Neoral formulation of CsA vs TAC (the other studies used the Sandimmune formulation of CsA). Our outcomes were similar, but notably we found that TAC decreased circulating antibody formation compared with CsA. This may have some impact on the development of transplant coronary artery disease, but long-term results on this complication are still pending in all the clinical trials mentioned. It may seem that TAC has advantages over CsA, but at this time, a majority of programs around the world use cyclosporine. I believe that until TAC demonstrates superiority over CsA (ie, less transplant coronary disease) it will be used as a second agent.
Corticosteroids such as prednisone have long been used in many immunosuppression protocols. Many programs wean prednisone either early or late (6 months) after transplant to avoid the long-term complication. The majority of transplant programs continue to use prednisone in the long-term.
The use of MMF has been recently demonstrated to have outcome benefits over azathioprine in a large multicenter trial. I believe more programs will use this drug as it becomes more available. If MMF is not available, then I would use azathioprine, which is adequate therapy.
A final note is that the use of cytolytic (ie, OKT3 monoclonal antibody) induction therapy, given immediately after surgery, seems to be losing interest, with only a few programs continuing its use. There has never been a randomized study supporting the use of cytolytic induction therapy. There are many new immunosuppressive medications becoming available which will change the landscape of our protocols in the future. Sirolimus, anti-IL2 receptor monoclonal antibodies, and FTY-720, to name a few, are promising and are currently in clinical trials.
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