Taylor D O, Barr M L, Radovancevic B, Renlund D G, Mentzer R M, Smart F W, Tolman D E, Frazier O H, Young J B, VanVeldhuisen P
Department of Medicine, University of Utah, Salt Lake City, USA.
J Heart Lung Transplant. 1999 Apr;18(4):336-45. doi: 10.1016/s1053-2498(98)00060-6.
Tacrolimus-based immunosuppression seems safe and effective in liver and kidney transplantation. To assess the safety and efficacy of tacrolimus (TAC)-based immunosuppression after cardiac transplantation as well as the relative impact of tacrolimus on immunosuppression-related side effects such as hypertension and hyperlipidemia, we conducted a prospective, randomized, open-label, multicenter study of otherwise identical tacrolimus- and cyclosporine-based immunosuppressive regimens in adult patients undergoing cardiac transplantation.
Eighty-five adult patients (pts) at six United States cardiac transplant centers, undergoing their first cardiac transplant procedure, were prospectively randomized to receive either TAC-based (n = 39) or cyclosporine (CYA)-based (n = 46) immunosuppression. All pts received a triple-drug protocol with 15 pts (18%) receiving peri-operative OKT3 to delay TAC/CYA due to pre-transplant renal dysfunction. Endomyocardial biopsies were performed at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 24, and 52. The study duration was 12 months.
Patients were mostly male (87%) Caucasian (90%) with a mean age of 54 years and primary diagnoses of coronary artery disease (55%) and idiopathic dilated cardiomyopathy (41%). There were no significant demographic differences between groups. Patient and allograft survival were not different in the two groups. The probability and overall incidence of each grade of rejection, whether treated or not, and the types of treatment required did not differ between the groups. At baseline and through 12 months of follow-up, chemistry and hematology values were similar between the groups except serum cholesterol was higher in the CYA group at 3, 6, and 12 months (239 vs 205 mg/dL, 246 vs 191 mg/dL, 212 vs 186 mg/dL, respectively, p < 0.001). Likewise, LDL-cholesterol, HDL-cholesterol and triglycerides were significantly higher in the CYA group. More CYA patients received therapy for hypercholesterolemia (71% vs 41% at 12 months, p = 0.01). There were no significant differences in renal function, hyperglycemia, hypomagnesemia, or hyperkalemia during the first 12 months. More CYA patients developed new-onset hypertension requiring pharmacologic treatment (71% vs 48%, p = 0.05). The incidence of infection was the same for the two groups (2.6 episodes/pt/12 month follow-up).
Tacrolimus-based immunosuppression seems effective for rejection prophylaxis during the first year after cardiac transplantation and is associated with less hypertension and hyperlipidemia and no difference in renal function, hyperglycemia or infection incidence when compared to cyclosporine-based immunosuppression.
基于他克莫司的免疫抑制在肝移植和肾移植中似乎是安全有效的。为了评估心脏移植后基于他克莫司（TAC）的免疫抑制的安全性和有效性，以及他克莫司对免疫抑制相关副作用（如高血压和高脂血症）的相对影响，我们对接受心脏移植的成年患者进行了一项前瞻性、随机、开放标签、多中心研究，比较了基于他克莫司和环孢素的免疫抑制方案，其他方面均相同。
美国六个心脏移植中心的85名成年患者（pts），接受首次心脏移植手术，被前瞻性随机分为接受基于TAC的免疫抑制组（n = 39）或基于环孢素（CYA）的免疫抑制组（n = 46）。所有患者均接受三联药物方案，15名患者（18%）因移植前肾功能不全接受围手术期OKT3以延迟TAC/CYA使用。在第1、2、3、4、6、8、10、12、24和52周进行心内膜心肌活检。研究持续时间为12个月。
患者大多为男性（87%）、白种人（90%），平均年龄54岁，主要诊断为冠状动脉疾病（55%）和特发性扩张型心肌病（41%）。两组之间在人口统计学上无显著差异。两组患者和移植物存活率无差异。各等级排斥反应的概率和总体发生率，无论是否接受治疗，以及所需治疗类型在两组之间无差异。在基线和随访12个月期间，两组之间的化学和血液学值相似，但CYA组在3、6和12个月时血清胆固醇较高（分别为239 vs 205 mg/dL、246 vs 191 mg/dL、212 vs 186 mg/dL，p < 0.001）。同样，CYA组的低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和甘油三酯显著更高。更多CYA患者接受了高胆固醇血症治疗（12个月时为71% vs 41%，p = 0.01）。在最初12个月期间，肾功能、高血糖、低镁血症或高钾血症无显著差异。更多CYA患者发生需要药物治疗的新发高血压（71% vs 48%，p = 0.05）。两组感染发生率相同（2.6次/患者/12个月随访）。
与基于环孢素的免疫抑制相比，基于他克莫司的免疫抑制在心脏移植后第一年预防排斥反应似乎有效，且与较少的高血压和高脂血症相关，在肾功能、高血糖或感染发生率方面无差异。
