Forum ekspertów
Advances of immunosuppressive therapy for heart transplantation

The immunosuppressive therapy after heart transplantation has undergone dramatic changes during the last decade [1, 2]. Although triple-drug therapy consisting of corticosteroids, calcineurin inhibitor and anti-proliferative agent remains the mainstem of typical immunosuppression, several new drugs were developed which showed better safety and superior anti-rejection efficacy. Almost all centers replaced azathioprine with mycophenolate mofetil for maintenance immunosuppression, nearly half of heart transplant recipients receive tacrolimus instead of cyclosporine, and an increasing number of patients are treated with, perhaps the most promising class of anti-proliferative agents, mTOR inhibitors [2, 3]. The empiric use of statin therapy, aggressive preconditioning of allosensitized recipients and the increased use of selective induction, are only few examples of changes in clinical practices that distinguished this remarkable decade of cardiac transplantation.
Anti-Proliferative Agents
The widespread use of mycophenolate mofetil (MMF) was one of the most remarkable changes that occurred during the last decade. Introduced in mid-1990s, MMF has almost completely replaced azathioprine (AZA, Imuran^®) from maintenance immunosuppresion in nearly all heart transplant recipients in the United States (Fig. 1) [2, 3]. In 2003, seventy six percent of heart transplant recipients received MMF as part of the maintenance protocol compared to only 17% in 1995, Fig. 1. The unique ability of MMF to selectively inhibit lymphocyte proliferation without overt bone marrow depression frequently seen in patients treated with AZA, was the first observation which led to the replacement of AZA with MMF. Two subsequent large, randomized efficacy trials comparing MMF to AZA [4, 5] showed other important advantages of MMF. The use of MMF demonstrated superior anti-rejection efficacy and improved 1- and 3-year survival, correlating with 35% reduction in mortality [3, 4]. MMF was also associated with later onset of transplant-related coronary vasculopathy (CAV) and its slower progression. Prevention of CAV development was demonstrated both in serial intravascular ultrasound studies [6], and in a large retrospective series of 26,000 HT recipients reported to UNOS [3]. The only major limitation to MMF therapy are frequent gastrointestinal side effects and opportunistic infections. A new enteric-coated form of MMF, (EC-MCS, enteric coated...


View full text...