Helmschrott Matthias, Beckendorf Jan, Akyol Ceylan, Ruhparwar Arjang, Schmack Bastian, Erbel Christian, Gleissner Christian A, Akhavanpoor Mohammadreza, Ehlermann Philipp, Bruckner Tom, Katus Hugo A, Doesch Andreas O
Department of Cardiology, Angiology, Pneumology, University of Heidelberg, Heidelberg, Germany.
Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany.
Drug Des Devel Ther. 2014 Sep 9;8:1307-14. doi: 10.2147/DDDT.S68542. eCollection 2014.
The use of tacrolimus (TAC) in patients after heart transplantation (HTX) has increased over the last few years.
In this retrospective study, we evaluated the effects of a TAC (conventional and extended-release TAC)-based immunosuppressive therapy regarding rejection profile in comparison to a cyclosporine A (CSA)-based regimen in patients after HTX.
The data of 233 patients who underwent HTX at the Heidelberg Heart Transplantation Center from May 1998 until November 2010 were retrospectively analyzed. Primary immunosuppressive therapy was changed from a CSA (n=114) to a TAC (n=119)-based regimen in February 2006 according to center routine. Follow-up period was 2 years post-HTX. Primary endpoint was time to first biopsy-proven rejection requiring therapy. In all patients, routine follow-up at the Heidelberg Heart Transplantation Center was mandatory.
Multivariate risk factor analysis regarding time to first rejection episode showed no statistically significant differences regarding recipient age, donor age, recipient sex, donor sex, sex mismatch, ischemic time, and diagnosis leading to HTX between the two groups (all P= not statistically significant). Time to first biopsy-proven rejection was significantly longer in the TAC group (intention-to-treat analysis, n=233, log-rank test P<0.0001; per-protocol analysis, n=150, log-rank test P=0.0003). In patients who underwent a change of primary immunosuppression (n=49), a significantly longer time to first biopsy-proven rejection was also found in the primary TAC subgroup (log-rank test P=0.0297). Further subgroup analysis in the TAC subgroups showed no statistically significant differences in time to biopsy-proven rejection under extended-release TAC compared to conventional TAC (intention-to-treat analysis, log-rank test P=0.1736).
Our study demonstrated that a TAC-based primary immunosuppressive therapy is superior to a CSA-based immunosuppressive regimen in patients after HTX regarding time to first biopsy-proven rejection.
在过去几年中，心脏移植（HTX）术后患者使用他克莫司（TAC）的情况有所增加。
在这项回顾性研究中，我们评估了以TAC（传统型和缓释型TAC）为基础的免疫抑制治疗与以环孢素A（CSA）为基础的治疗方案相比，对HTX术后患者排斥反应情况的影响。
回顾性分析了1998年5月至2010年11月在海德堡心脏移植中心接受HTX的233例患者的数据。根据中心常规，2006年2月将主要免疫抑制治疗从CSA（n = 114）改为以TAC（n = 119）为基础的治疗方案。随访期为HTX术后2年。主要终点是首次经活检证实需要治疗的排斥反应的时间。在所有患者中，海德堡心脏移植中心的常规随访是强制性的。
关于首次排斥反应发作时间的多因素风险分析显示，两组在受者年龄、供者年龄、受者性别、供者性别、性别不匹配、缺血时间和导致HTX的诊断方面无统计学显著差异（所有P =无统计学意义）。TAC组首次经活检证实的排斥反应时间明显更长（意向性分析，n = 233，对数秩检验P <0.0001；符合方案分析，n = 150，对数秩检验P = 0.0003）。在接受主要免疫抑制治疗改变的患者（n = 49）中，主要TAC亚组中首次经活检证实的排斥反应时间也明显更长（对数秩检验P = 0.0297）。TAC亚组中的进一步亚组分析显示，与传统TAC相比，缓释TAC下经活检证实的排斥反应时间无统计学显著差异（意向性分析，对数秩检验P = 0.1736）。
我们的研究表明，在HTX术后患者中，以TAC为基础的主要免疫抑制治疗在首次经活检证实的排斥反应时间方面优于以CSA为基础的免疫抑制方案。
