Immunosuppression for heart transplantation: where are we now?

Abstract

The success of cardiac transplantation is largely attributable to the development of effective immunosuppressive regimens. The introduction of calcineurin inhibitors was pivotal in reducing the frequency of acute rejection and improving early survival. Newer agents, including mycophenolate mofetil (MMF) and proliferation-signal inhibitors, have shown promise in further reducing acute-rejection rates and, notably, reducing the frequency of cardiac allograft vasculopathy, which limits long-term graft survival. The introduction of first-year intravascular ultrasonography results as a surrogate marker for outcome after cardiac transplantation has helped assessment of the efficacy of immunosuppressive medications. Proliferation-signal inhibitors and MMF were shown by this imaging method to reduce cardiac allograft vasculopathy. The combination of these drugs, in tandem with the weaning of patients off calcineurin inhibitors, has been shown to reverse calcineurin-inhibitor-related nephrotoxic effects. A randomized trial that compared three of the more common immunosuppressive regimens suggested that tacrolimus and MMF are associated with a reduction in the frequency of rejection episodes that require treatment and have the fewest adverse effects. Finally, the use of statins has brought added benefit to immunosuppressive regimens by improving outcomes after cardiac transplantation, reportedly because of an immunomodulatory property. Promising newer immunosuppressive agents await clinical trials. This review presents an overview of the emerging data on immunosuppressive therapy for cardiac transplantation.