Optimizing Immunosupression in Patients Following Heart Transplantation
Mitchell, Joshua D.
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BACKGROUND: Effective immunosuppression is necessary for long-term survival following heart transplantation, but it is also associated with a multitude of adverse effects. Protocols have emerged to attempt to optimize the risk-to-benefit ratio of immunosuppression. We reviewed our center's experience with two such protocols: tapering corticosteroids following heart transplantation and administering basiliximab as an induction agent. METHODS: We reviewed the records of all cardiac transplant recipients at our center between 1988 and August 2004. Patients treated with traditional triple therapy immunosuppression (cyclosporine, azathioprine, and prednisone; CAP) were compared to a similar group of patients treated with a goal of rapid (within 6 months) steroid taper and discontinuation (CAPT). Patients who received basiliximab as an induction agent were compared to a historical control group of patients who received a similar immunosuppressive protocol without basiliximab induction. RESULTS: Fifty-seven percent of the patients in the CAPT group were successfully withdrawn from steroids at six months post-transplantation. This group had a decreased freedom from acute rejection (p<0.01) and increased frequency of acute rejection (p<0.01) when compared to the CAP group. There was, however, no difference in freedom from transplant coronary artery disease (p=0.53). The CAPT group enjoyed an increased freedom from malignancy (p=0.01) and trended towards a decreased frequency of infection (p=0.10) and improved survival (p=0.06) when compared to the CAP group.One hundred forty-five patients were included in the comparison between basiliximab and control. At one and two-years post-transplantation, no difference was found between groups in the rise of serum creatinine (p=0.29). Basiliximab induction decreased the frequency of acute rejection (p=0.02) and improved the freedom from first acute rejection episode (p<0.01) during the first two years after transplantation. It had no statistically significant effect on freedom from infection, malignancy, or overall survival in our cardiac transplant population (p=0.52, p=0.85,p=0.27 respectively). CONCLUSIONS: Steroid withdrawal was possible in 57% of patients at six months posttransplantation.The institution of an early steroid taper protocol improves the overall freedom from malignancies and may decrease the frequency of infection and prolong overall survival. Basiliximab induction does not affect renal function at mid-term follow-up; however, it decreases the frequency of acute rejection and increases the freedom from first acute rejection episode. It accomplishes this without decreasing the freedom from infection, malignancy, and transplant vasculopathy. Novel medications and treatment protocols provide an opportunity for transplant teams to continue to optimize immunosuppression while simultaneously minimizing side-effects.