TY - JOUR
T1 - Proliferation signal inhibitors in cardiac transplantation
AU - Gustafsson, Finn
AU - Ross, Heather J
PY - 2007/3
Y1 - 2007/3
N2 - PURPOSE OF REVIEW: Standard immunosuppression after cardiac transplantation includes a calcineurin inhibitor in combination with mycophenolate mofetil or azathioprine and corticosteroids. These agents have led to excellent outcomes but have shortcomings in terms of efficacy and toxicity. A new class of immunosuppressants, proliferation signal inhibitors, may meet some of these shortcomings.RECENT FINDINGS: The efficacy of the available proliferation signal inhibitors - sirolimus and its derivative everolimus - has been compared with azathioprine in three randomized clinical trials. Sirolimus or everolimus use was associated with lower rates of acute rejection and reduced development of chronic allograft vasculopathy. Sirolimus was not found to be superior to mycophenolate mofetil in a randomized trial. Proliferation signal inhibitors have been reported to be effective in refractory recurrent acute rejection. Nonrandomized studies have demonstrated that proliferation signal inhibitor-based immunosuppression enables recovery from renal dysfunction secondary to calcineurin inhibitor treatment. Proliferation signal inhibitor-based treatment is associated with a lower risk of malignancy than calcineurin inhibitor-based regimens. Proliferation signal inhibitors have significant adverse effects that may limit widespread use.SUMMARY: Proliferation signal inhibitors are important new immunosuppressive agents that have added considerably to the armamentarium allowing further tailored immunosuppression to individualize patient care after heart transplantation.
AB - PURPOSE OF REVIEW: Standard immunosuppression after cardiac transplantation includes a calcineurin inhibitor in combination with mycophenolate mofetil or azathioprine and corticosteroids. These agents have led to excellent outcomes but have shortcomings in terms of efficacy and toxicity. A new class of immunosuppressants, proliferation signal inhibitors, may meet some of these shortcomings.RECENT FINDINGS: The efficacy of the available proliferation signal inhibitors - sirolimus and its derivative everolimus - has been compared with azathioprine in three randomized clinical trials. Sirolimus or everolimus use was associated with lower rates of acute rejection and reduced development of chronic allograft vasculopathy. Sirolimus was not found to be superior to mycophenolate mofetil in a randomized trial. Proliferation signal inhibitors have been reported to be effective in refractory recurrent acute rejection. Nonrandomized studies have demonstrated that proliferation signal inhibitor-based immunosuppression enables recovery from renal dysfunction secondary to calcineurin inhibitor treatment. Proliferation signal inhibitor-based treatment is associated with a lower risk of malignancy than calcineurin inhibitor-based regimens. Proliferation signal inhibitors have significant adverse effects that may limit widespread use.SUMMARY: Proliferation signal inhibitors are important new immunosuppressive agents that have added considerably to the armamentarium allowing further tailored immunosuppression to individualize patient care after heart transplantation.
KW - Azathioprine/therapeutic use
KW - Calcineurin/adverse effects
KW - Calcineurin Inhibitors
KW - Cell Proliferation/drug effects
KW - Coronary Artery Disease/etiology
KW - Dose-Response Relationship, Drug
KW - Everolimus
KW - Graft Rejection/complications
KW - Heart Transplantation
KW - Humans
KW - Immunosuppressive Agents/adverse effects
KW - Mycophenolic Acid/analogs & derivatives
KW - Signal Transduction/drug effects
KW - Sirolimus/analogs & derivatives
U2 - 10.1097/HCO.0b013e328012545e
DO - 10.1097/HCO.0b013e328012545e
M3 - Review
C2 - 17284989
SN - 0268-4705
VL - 22
SP - 111
EP - 116
JO - Current Opinion in Cardiology
JF - Current Opinion in Cardiology
IS - 2
ER -