Proliferation signal inhibitors: a new substance class in immunosuppression after heart transplantation

Purpose of review Proliferation signal inhibitors (mammalian target of rapamycin inhibitors) are a relatively new class of immunosuppressive drugs with growing importance for the treatment of patients after heart transplantation. This review outlines the recent literature on mammalian target of rapamycin inhibitors in preclinical and clinical settings. Recent findings By means of double-blind randomized studies, proliferation signal inhibitors have proven to be associated with lower incidences of biopsy-proven acute rejection and fewer cytomegaly virus infections, which are both risk factors for cardiac allograft vasculopathy. Consequently, mammalian target of rapamycin inhibitors led to significant reduction of cardiac allograft vasculopathy up to 24 months after transplantation. In smaller, nonrandomized investigations, it was possible to reduce and even abandon calcineurin inhibitor medication, leading to an improvement of renal function without increasing incidences of rejection. Side effects of mammalian target of rapamycin inhibitors include hyperlipidemia, leukocytopenia, and higher susceptibility to bacterial infections in a dose-dependent manner. Summary Proliferation signal inhibitors are valuable tools for the clinician treating patients after heart transplantation. Their safety and efficacy for the use in combination with calcineurin inhibitors has been demonstrated in phase III clinical trials up to 24 months after transplantation. Randomized studies on reduced or even calcineurin inhibitor-free regimens are still warranted.