Dandel M, Jasaityte R, Lehmkuhl H, Knosalla C, Hetzer R
Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Barlin, Germany.
Transplant Proc. 2009 Jul-Aug;41(6):2585-8. doi: 10.1016/j.transproceed.2009.06.031.
Mycophenolate mofetil (MMF) is superior to azathioprine (AZA) in preventing allograft rejections episodes (ARE) early after heart transplantation (HTx). However, long-term efficacy and adverse events are barely known. We evaluated the long-term efficacy and safety, comparing patient outcomes with either MMF or AZA as components of maintenance immunosuppression regimens.
We evaluated all patients who underwent HTx between January 1994 and May 2003 and received the same induction immunosuppression followed by treatment with cyclosporine (CsA), prednisolone, and with either MMF or AZA. We analyzed the survival, number, and severity of ARE, development of coronary allograft vasculopathy (CAV), and main adverse effects (infections, tumors).
Patients receiving MMF (n = 137) showed a lower mortality rate than those treated with AZA (n = 121). There were significant differences between the groups for all parameters evaluated (P < .01). The prevalence of deaths was 18.3% in the MMF group and 47.9% in the AZA group. Biopsy-proven ARE greater than grade 1A and antirejection therapies per patient were lower among the MMF than the AZA group (0.20 vs 0.31 and 0.96 vs 1.24, respectively). Prevalence of coronary stenoses was 11.7% in the MMF group and 24.8% in the AZA group. Rate of extracutaneous and cutaneous malignancies was lower in the MMF than the AZA group (7.3% and 5.8% vs 18.2% and 9.1%, respectively). The prevalence of infections was higher in the MMF group. Patients who were switched during the first post-HTx year from AZA to MMF (n = 97) and thereafter received CsA plus MMF for >1 year also showed significantly better survival than those who remained on AZA treatment.
Among a cohort of patients being followed long term, MMF appeared to be highly efficient to prevent both ARE and the development of coronary artery stenoses. The use of MMF also significantly improved the survival of heart transplant recipients compared with AZA, despite a greater incidence of infections linked to MMF therapy.
在心脏移植（HTx）后早期预防同种异体移植排斥反应（ARE）方面，霉酚酸酯（MMF）优于硫唑嘌呤（AZA）。然而，其长期疗效和不良事件鲜为人知。我们评估了MMF或AZA作为维持免疫抑制方案组成部分时患者的长期疗效和安全性，并比较了患者的预后情况。
我们评估了1994年1月至2003年5月期间接受HTx且接受相同诱导免疫抑制治疗，随后接受环孢素（CsA）、泼尼松龙以及MMF或AZA治疗的所有患者。我们分析了患者的生存率、ARE的数量和严重程度、冠状动脉同种异体血管病变（CAV）的发生情况以及主要不良反应（感染、肿瘤）。
接受MMF治疗的患者（n = 137）的死亡率低于接受AZA治疗的患者（n = 121）。在所有评估参数方面，两组之间存在显著差异（P < 0.01）。MMF组的死亡率为18.3%，AZA组为47.9%。MMF组中经活检证实的大于1A级的ARE以及每位患者的抗排斥治疗次数均低于AZA组（分别为0.20对0.31以及0.96对1.24）。MMF组冠状动脉狭窄的发生率为11.7%，AZA组为24.8%。MMF组皮肤外和皮肤恶性肿瘤的发生率低于AZA组（分别为7.3%和5.8%对18.2%和9.1%）。MMF组感染的发生率较高。在HTx后的第一年从AZA转换为MMF（n = 97），此后接受CsA加MMF治疗超过1年的患者，其生存率也显著高于继续接受AZA治疗的患者。
在一组长期随访的患者中，MMF似乎在预防ARE和冠状动脉狭窄方面非常有效。与AZA相比，使用MMF也显著提高了心脏移植受者的生存率，尽管与MMF治疗相关的感染发生率更高。
