EUROPEAN MULTICENTER TACROLIMUS (FK506) HEART PILOT-STUDY - ONE-YEAR RESULTS - EUROPEAN TACROLIMUS MULTICENTER HEART-STUDY GROUP

Background: Tacrolimus (FK506) may represent a major advance in the ma nagement of allograft rejection after solid organ transplantation. In August 1994 a European heart transplantation pilot study was initiated to assess the efficacy and safety of tacrolimus when administered exc lusively through an oral route. Methods: Eighty-two heart transplant r ecipients were randomized to treatment (2:1 ratio) with either tacroli mus- (n = 54) or cyclosporine-based therapy (n = 28). Results: No sign ificant differences were evident between the two treatment groups in e ither rejection or survival rates at 1 year. Kaplan-Meier estimates of the freedom from rejection were 26.3% and 18.5%, respectively, for th e tacrolimus and cyclosporine treatment groups (p=.444). Survival rate s were 79.6% and 92.9% (p =.125). At 3 of the 5 centers, patients rece ived antithymocyte globulin during the immediate postoperative period and fared better than those who did not (with acute rejection-free rat es of 49.2% and 26.7% for tacrolimus and cyclosporine, respectively [p =.080], as opposed to 7.1% and 8.3% [p =.965]; patient survival rates of 84.6% and 93.3% [p =.382] vs 75.0% and 92.3% [p =.243]). The overa ll rates of infection, impaired renal function (31.5% vs 21.4%), and g lucose intolerance (7.0% vs 4.3%) did not differ significantly between the tacrolimus and cyclosporine treatment groups. Tacrolimus seemed t o possess an advantage with regard to a reduced requirement for antihy pertensive therapy (59.5% vs 87.5%, p =.025). Conclusions: Immunosuppr ession with oral tacrolimus provides a viable alternative to treatment with cyclosporine, particularly when administered in conjunction with antibody therapy. Further studies are warranted to optimize the admin istration of tacrolimus in this indication.