BACKGROUND:

Tacrolimus (TAC) monotherapy has been compared to TAC and mycophenolate mofetil (MMF) in the randomized Tacrolimus in Combination, Tacrolimus Alone Compared (TICTAC) trial. Long term results are now reported.

METHODS:

Demographics are presented with descriptive statistics. Time to event was determined with Kaplan-Meier plots and Mantel-Cox Logrank statistics used to compare groups.

RESULTS:

One hundred and forty-seven (98 %) of the initial 150 TICTAC trial patients had long-term follow-up data available. The median follow-up was 13.4 years (interquartile range 7.2-15.1 years). Post-transplant survival at 5, 10 and 15 years in the TAC monotherapy group was 84.5 %, 66.9 %, and 52.7 %, and 94.4 %, 78.2 % and 56.1 % for patients randomized to TAC / MMF (p = 0.19 logrank). The freedom from cardiac allograft vasculopathy (≥grade 1) was 100 %, 87.5 %, 69.3 % and 46.5 % at 1, 5, 10 and 15 years in the monotherapy group and 100 %, 76.9 %, 68.1 % and 54.4 % in the TAC/MMF group respectively (p = 0.96 logrank). Crossover of treatment assignment did not alter these findings. The freedom from dialysis or renal replacement was 92.8 %, 84.2 % and 68.4 % for TAC monotherapy patients versus 100 %, 93.4 % and 82.3 % for TAC/MMF patients at 5, 10 and 15-years post-transplant (p = 0.15 logrank).

CONCLUSIONS:

Patients randomized to TAC/ MMF with 8-week steroid weaning had comparable outcomes to those with similar steroid regimen but discontinuation of MMF at 2 week post-transplant. The best outcomes were noted for patients initiated on TAC/ MMF including those where MMF was discontinued for intolerance. Both strategies are reasonable alternatives for patients post heart transplant.

CONDENSED ABSTRACT:

Tacrolimus monotherapy was compared to TAC and mycophenolate mofetil without long term steroids in the randomized Tacrolimus in Combination, Tacrolimus Alone Compared (TICTAC) trial. Post-transplant survival at 5, 10 and 15 years in the TAC monotherapy group was 84.5%, 66.9 %, and 52.7 %, and 94.4 %, 78.2 % and 56.1 % for patients randomized to TAC / MMF (p = 0.19 logrank). Cardiac allograft vasculopathy and kidney failure were similar between groups. Immunosuppression should be individualized to avoid over treating some patients while undertreating others.