A Randomized Comparison of an Immunosuppressive Strategy Using Tacrolimus and Cyclosporine in Black Heart Transplant Recipients M.R. Mehra, P.A. Uber, M.H. Park, A.K. Prasad, and R.L. Scott B LACK recipient race has been demonstrated to confer poor clinical outcome in cyclosporine-treated heart transplant recipients. 1 Newer advances in immunosuppres- sion such as cyclosporine microemulsion, tacrolimus, and mycophenolate mofetil have all demonstrated improved efficacy in several investigations; however, blacks have been significantly underrepresented in these trials. 2,3 Thus, it is not feasible to extract relevant information regarding blacks from such investigations, in particular whether these newer agents offer incremental efficacy in this higher risk cohort that abrogates the traditional poor clinical outcome. PATIENTS AND METHODS We conducted a prospective clinical trial in 42 black adult primary heart transplant recipients who were randomized to receive either tacrolimus (n = 20) or cyclosporine microemulsion (n = 22). Tacrolimus was begun orally within 12 hours of transplantation. Target trough levels were 15 to 20 ng/mL for first 3 months, dropping to 10 to 15 ng/mL thereafter. Whole blood concentrations of tacrolimus were assessed using the Abbott Imx assay. Intrave- nous cyclosporine was started within 12 hours postoperation and transitioned to cyclosporine microemulsion within 24 to 36 hours. Target cyclosporine trough levels were 300 ng/mL for the first 3 months, decreasing to 200 to 250 ng/mL thereafter (HPLC). Standard doses of mycophenolate mofetil were used (2 to 3 g/d) and steroids were tapered immediately following initiation accord- ing to our standard protocol but only after therapeutic levels of calcineurin inhibitors were achieved. Dose adjustments were made to achieve the target trough levels and follow up was maintained for at least 1 year in all patients. HMG-COA reductase inhibitors were given unless contraindicated. The efficacy variables examined between the two groups included allograft rejection (treated rejections and rejections with hemody- namic compromise) and allograft or patient survival. Safety param- eters assessed included treated infections and drug withdrawals. Nonimmunologic complications including treated hypertension, hyperlipidemia requiring therapy, diabetes mellitus (new onset or worsened), and renal dysfunction were also evaluated. Kaplan- Meier event-free survival plots were developed and analyzed for the major efficacy parameters. RESULTS Baseline Data No differences between the two groups were noted with respect to recipient age and gender; donor age, gender, and ethnicity; or cold ischemic time. Similarly, rates of induction cytolytic therapy, elevated panel reactive antibodies, posi- tive T-cell crossmatch, and number of HLA matches were equally distributed among cyclosporine- and tacrolimus- treated patients. Allograft Rejection Episodes of allograft rejection (number per patient in 12 months) requiring treatment were significantly higher in cyclosporine-treated patients than tacrolimus (1.3  1.6 versus 0.65  1, P = .01). Similarly, episodes of rejection with hemodynamic compromise (number/patient/year) de- fined as decreased ejection fraction  0.35 or need for inotropic or mechanical ventricular support, were signifi- cantly reduced in the tacrolimus arm compared to cyclo- sporine (0.35  0.19 vs 1.1  1.3, P = .02). Infections At 1 year, rates of any episode of infection requiring hospitalization for treatment was no different in cyclospo- rine and tacrolimus arms (0.48  0.52 vs 0.53  0.51, P = NS). In assessing the number of infections per patient, although no statistically significant differences were noted in the two groups, trends suggested a higher infection frequency in tacrolimus-treated patients (0.58  0.6 versus 1.1  1.6, P = .1). Cytomegalovirus infections requiring intravenous treatment were also statistically similar among cyclosporine- and tacrolimus-treated patients (0.11  0.30 vs 0.27  0.46, P = NS). Survival Analysis Actuarial curves depicting freedom from treated rejections, freedom from treated infections, and graft or patient sur- vival, in cyclosporine and tacrolimus treated study groups are shown in Fig 1. In summary, these plots demonstrate a decrease in treated rejections and improved survival in the tacrolimus group, while showing no increases in infection. From The Ochsner Cardiomyopathy and Heart Transplanta- tion Center, Ochsner Medical Institutions, New Orleans, Louisi- ana, USA. Address reprint requests to Mandeep R. Mehra, MD, BH-326, 1514 Jefferson Highway, New Orleans, LA 70121. E-mail: mmehra@ochsner.org. 0041-1345/01/$–see front matter © 2001 by Elsevier Science Inc. PII S0041-1345(00)02611-7 655 Avenue of the Americas, New York, NY 10010 1606 Transplantation Proceedings, 33, 1606–1607 (2001)