SINGLE-CENTER RANDOMIZED TRIAL COMPARING TACROLIMUS (FK506) AND CYCLOSPORINE IN THE PREVENTION OF ACUTE MYOCARDIAL REJECTION

Background: To compare the efficacy and safety of tacrolimus and cyclo sporine in heart transplantation, this single-center, prospective, ran domized, open-label clinical trial was undertaken. Methods: Seventy-th ree adult patients were randomly assigned at the time of transplantati on to receive either tacrolimus (n = 43) or cyclosporine (n = 30) as t he primary immunosuppressant. Ten of the 43 patients in the tacrolimus group received the drug intravenously in the perioperative period; al l other patients received only oral tacrolimus. Results: With a mean f ollow-up of 27 months, patient survival rates (tacrolimus 83%, cyclosp orine 81%) were similar. Fewer patients experienced acute rejection in the tacrolimus group (79%) than in the cyclosporine group (100%), but the difference was not statistically significant. The number of infec tions and dialysis and insulin requirements were similar for the 2 tre atment groups, but the proportion of patients requiring multidrug anti hypertensive regimens was lower in the tacrolimus group (12.5% vs 50.0 % at month 6; p =.025). The interpatient variance in pharmacokinetic p arameters in a subset of 10 patients was much higher after the first o ral dose of tacrolimus than at steady-state leg, first-dose time at wh ich maximal concentration is reached (t(max)): 3.5 +/- 2.5h, steady-st ate t(max): 2.0 +/- 0.7h), and patients treated with intravenous tacro limus (n = 13) rather than oral tacrolimus (n = 30) reached target con centrations faster and with less interpatient variability (eg, at day 0: 9.72 +/- 10.9 ng/mL intravenously vs 3.31 +/- 8.1 orally). Conclusi ons: Tacrolimus was associated with similar efficacy and safety profil es compared with cyclosporine. The higher interpatient variance in abs orption associated with oral tacrolimus during the first few days afte r transplantation would suggest that intravenous tacrolimus should be used during the perioperative period.