FK506 EFFECTIVENESS IN REDUCING ACUTE REJECTION AFTER HEART-TRANSPLANTATION - A PROSPECTIVE RANDOMIZED STUDY

Background: Tacrolimus (FK506) has recently become available clinicall y as an alternative to cyclosporine-based immunosuppression. This stud y reports the middle-term results of a prospective, randomized trial t hat compared FK506 with cyclosporine-based immunosuppression in heart transplant recipients. Methods: Twenty-five consecutive patients were randomized at a 2:1 ratio into two groups, one of which received FK506 (15 patients), the other cyclosporine (10 patients). Both groups rece ived similar concomitant immunosuppression. The patients were followed up for 12 months. The following outcome parameters were analyzed: sur vival, rejection and infection rate, lymphocyte subsets, new-onset dia betes, renal and hepatic function, hypertension, right-sided heart cat heterization data, graft coronary artery disease, and neurologic side effects. Results: The mortality rate (two patients) in the FK506 group was 13% versus 0% in the cyclosporine group (p = NS). The two deaths were the consequences of early infections and higher doses of FK506. F rom the outset, the FK506 group presented a lower prevalence of acute rejection, a lower requirement for rejection treatments and a higher i ncidence of infections. Accordingly, we reduced overall immunosuppress ion for the last seven patients in the FK506 group; the decrease in FK 506 and prednisone dosage led to a decrease in the early infection rat e without an increase in the rejection rate. There was no difference b etween the two groups in diabetes incidence, renal and hepatic functio n, right-sided heart catheterization data, or coronary angiograms. Hyp ertension was less frequent and milder in the FK506 group. Conclusions : This experience suggests that FK506 can be safely used in heart tran splantation It can decrease the frequency of rejection episodes. Low-d ose administration allows a lower infection rate without an increase i n rejection. With a protocol of delayed starting and low dosing, side effects such as renal toxicity, hypertension, and neurologic toxicity seem to be unlikely. Further studies are needed to establish the exact dosage and therapeutic levels of the drug.