Kaczmarek Ingo, Ertl Bjoern, Schmauss Daniel, Sadoni Sebastian, Knez Andreas, Daebritz Sabine, Meiser Bruno, Reichart Bruno
Department of Cardiac Surgery, Ludwig Maximilian University, Grosshadern, Munich, Germany.
J Heart Lung Transplant. 2006 May;25(5):550-6. doi: 10.1016/j.healun.2006.01.003. Epub 2006 Apr 11.
The impact of long-term mycophenolate mofetil (MMF) treatment on the development of cardiac allograft vasculopathy (CAV) after heart transplantation is an area of much recent interest. This study analyzed the effects of various immunosuppressive combinations, including cyclosporine (CsA), azathioprine (Aza), tacrolimus (Tac) and MMF, on the time of onset, extent and progression of CAV.
Two hundred seventy-three consecutive heart transplant recipients (mean age: 51.2 +/- 12.2 years; mean follow-up: 6.8 +/- 1.9 years) were examined by coronary angiography on a yearly basis between 1995 and 2003. The extent of CAV was evaluated using a scoring system based on the severity of vessel stenosis. The onset of CAV was analyzed using Kaplan-Meier estimates and the log rank test for four treatment combinations, CsA/Aza (n = 47, 17.2%), CsA/MMF (n = 26, 9.5%), Tac/Aza (n = 62, 22.7%) and Tac/MMF (n = 138, 50.5%), and for the primary and the secondary immunosuppressants alone.
The rate of freedom from CAV at 5 years was 47% with CsA/Aza, 66% with CsA/MMF, 60% with Tac/Aza and 70% with Tac/MMF. After 5 years, the Tac/MMF group showed a significantly lower incidence of CAV than the CsA/Aza group (log rank 7.58, p = 0.0059). CsA (n = 73) was compared with Tac (n = 200) and MMF (n = 164) with Aza (n = 109): the rate of freedom from CAV was 51.2% in CsA patients vs 66.1% in Tac patients (log rank 5.7, p = 0.017), and 54.6% in Aza patients vs 67% in MMF patients (log rank 4.36, p = 0.037). Multivariate Cox regression analysis revealed that MMF decreased the incidence of CAV significantly (p = 0.041). In this patient cohort, Tac or CsA medication was not an independent risk factor for incidence of CAV nor for decreased survival.
The choice of immunosuppression has an impact on the incidence of CAV. In terms of prevention of CAV, MMF is superior to Aza in either combination. A trend toward improved survival in MMF patients was noted. The lower number of rejection episodes in the MMF groups may have contributed to these results.
心脏移植后长期使用霉酚酸酯（MMF）治疗对心脏移植血管病变（CAV）发展的影响是近期备受关注的领域。本研究分析了包括环孢素（CsA）、硫唑嘌呤（Aza）、他克莫司（Tac）和MMF在内的各种免疫抑制组合对CAV发病时间、范围和进展的影响。
1995年至2003年间，每年对273例连续的心脏移植受者（平均年龄：51.2±12.2岁；平均随访时间：6.8±1.9年）进行冠状动脉造影检查。使用基于血管狭窄严重程度的评分系统评估CAV的范围。采用Kaplan-Meier估计法和对数秩检验分析四种治疗组合（CsA/Aza，n = 47，17.2%；CsA/MMF，n = 26，9.5%；Tac/Aza，n = 62，22.7%；Tac/MMF，n = 138，50.5%）以及单独使用的主要和次要免疫抑制剂对CAV发病情况的影响。
CsA/Aza组5年时无CAV的发生率为47%，CsA/MMF组为66%，Tac/Aza组为60%，Tac/MMF组为70%。5年后，Tac/MMF组的CAV发生率显著低于CsA/Aza组（对数秩7.58，p = 0.0059）。比较使用CsA（n = 73）与Tac（n = 200）以及MMF（n = 164）与Aza（n = 109）的情况：CsA患者无CAV的发生率为51.2%，Tac患者为66.1%（对数秩5.7，p = 0.017）；Aza患者为54.6%，MMF患者为67%（对数秩4.36，p = 0.037）。多因素Cox回归分析显示，MMF显著降低了CAV的发生率（p = 0.041）。在该患者队列中，使用Tac或CsA药物既不是CAV发生率的独立危险因素，也不是生存降低的独立危险因素。
免疫抑制方案的选择对CAV的发生率有影响。就预防CAV而言，MMF在任何一种组合中都优于Aza。注意到MMF患者有生存改善的趋势。MMF组排斥反应发作次数较少可能促成了这些结果。
