Department of Cardiology, Cleveland Clinic Heart, Vascular and Thoracic Institute, Cleveland, Ohio.
Division of Cardiology, Newark Beth Israel Medical Center, Heart Failure Treatment and Transplant Program, Newark, New Jersey.
J Heart Lung Transplant. 2023 Jun;42(6):838-845. doi: 10.1016/j.healun.2023.01.016. Epub 2023 Feb 8.
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.
Demographics are presented with descriptive statistics. Time to event was determined with Kaplan-Meier plots and Mantel-Cox Logrank statistics used to compare groups.
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).
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.
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.
他克莫司（TAC）单药治疗已在随机 TAC 联合、TAC 单药比较（TICTAC）试验中与 TAC 和吗替麦考酚酯（MMF）进行了比较。现在报告了长期结果。
用描述性统计方法介绍人口统计学数据。用 Kaplan-Meier 图和 Mantel-Cox Logrank 统计来确定时间事件，并用于比较组。
初始 150 例 TICTAC 试验患者中有 147 例（98%）有长期随访数据。中位随访时间为 13.4 年（四分位间距 7.2-15.1 年）。TAC 单药治疗组的移植后 5、10 和 15 年的存活率分别为 84.5%、66.9%和 52.7%，而随机接受 TAC/MMF 治疗的患者分别为 94.4%、78.2%和 56.1%（p=0.19 logrank）。单药治疗组在移植后 1、5、10 和 15 年的无心脏移植物血管病（≥1 级）的比例分别为 100%、87.5%、69.3%和 46.5%，而 TAC/MMF 组的比例分别为 100%、76.9%、68.1%和 54.4%（p=0.96 logrank）。治疗方案的交叉不会改变这些发现。TAC 单药治疗组的无透析或肾替代治疗的比例分别为 92.8%、84.2%和 68.4%，而 TAC/MMF 组的比例分别为 100%、93.4%和 82.3%（p=0.15 logrank）。
在随机 TICTAC 试验中，接受 8 周类固醇逐渐减量的 TAC/MMF 治疗的患者与接受类似类固醇方案但在移植后 2 周停用 MMF 的患者相比，具有可比的结局。对于接受 TAC/MMF 治疗的患者，包括因不耐受而停用 MMF 的患者，最好的结局是开始接受 TAC/MMF 治疗的患者。这两种策略都是心脏移植后患者的合理替代方案。
