依维莫司对心脏移植后血管病变的影响——一项随机、多中心试验的结果。
Effect of everolimus introduction on cardiac allograft vasculopathy--results of a randomized, multicenter trial.
机构信息
Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
出版信息
Transplantation. 2011 Jul 27;92(2):235-43. doi: 10.1097/TP.0b013e31822057f1.
BACKGROUND
Everolimus reduces the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant (HTx) recipients, but the influence on established CAV is unknown.
METHODS
In this Nordic Certican Trial in Heart and lung Transplantation substudy, 111 maintenance HTx recipients (time post-HTx 5.8 ± 4.3 years) randomized to everolimus+reduced calcineurin inhibitor (CNI) or standard CNI had matching (intravascular ultrasound) examinations at baseline and 12 months allowing accurate assessment of CAV progression.
RESULTS
No significant difference in CAV progression was evident between the treatment groups (P = 0.30). When considering patients receiving concomitant azathioprine (AZA) therapy (n = 39), CAV progression was attenuated with everolimus versus standard CNI (Δmaximal intimal thickness 0.00 ± 0.04 and 0.04 ± 0.04 mm, Δpercent atheroma volume 0.2% ± 3.0% and 2.6% ± 2.5%, and Δtotal atheroma volume 0.25 ± 14.1 and 19.8 ± 20.4 mm(3), respectively [P < 0.05]). When considering patients receiving mycophenolate mofetil (MMF), accelerated CAV progression occurred with everolimus versus standard CNI (Δmaximal intimal thickness 0.06 ± 0.12 vs. 0.02 ± 0.06 mm and Δpercent atheroma volume 4.0% ± 6.3% vs. 1.4% ± 3.1%, respectively; P < 0.05). The levels of C-reactive protein and vascular cell adhesion molecule-1 declined significantly with AZA+everolimus, whereas MMF+everolimus patients demonstrated a significant increase in levels of C-reactive protein, vascular cell adhesion molecule-1, and von Willebrand factor.
CONCLUSIONS
Conversion to everolimus and reduced CNI does not influence CAV progression among maintenance HTx recipients. However, background immunosuppressive therapy is important as AZA+everolimus patients demonstrated attenuated CAV progression and a decline in inflammatory markers, whereas the opposite pattern was seen with everolimus+MMF. The different effect of everolimus when combined with AZA versus MMF could potentially reflect hitherto unknown interactions.
背景
依维莫司可减少心脏移植（HTx）受者新发心脏移植物血管病（CAV）的进展，但对已建立的 CAV 的影响尚不清楚。
方法
在这项北欧心脏和肺移植临床试验的子研究中，111 名维持性 HTx 受者（HTx 后时间 5.8±4.3 年）随机分为依维莫司+减少钙调神经磷酸酶抑制剂（CNI）或标准 CNI 组，两组在基线和 12 个月时均进行了匹配的（血管内超声）检查，可准确评估 CAV 进展情况。
结果
两组间 CAV 进展无显著差异（P=0.30）。当考虑同时接受硫唑嘌呤（AZA）治疗的患者（n=39）时，与标准 CNI 相比，依维莫司可减轻 CAV 进展（最大内膜厚度差值分别为 0.00±0.04 和 0.04±0.04 mm，动脉粥样斑块体积百分比差值分别为 0.2%±3.0%和 2.6%±2.5%，总动脉粥样斑块体积差值分别为 0.25±14.1 和 19.8±20.4 mm3[P<0.05]）。当考虑接受吗替麦考酚酯（MMF）的患者时，与标准 CNI 相比，依维莫司会加速 CAV 进展（最大内膜厚度差值分别为 0.06±0.12 和 0.02±0.06 mm，动脉粥样斑块体积百分比差值分别为 4.0%±6.3%和 1.4%±3.1%，P<0.05）。依维莫司+AZA 组的 C 反应蛋白和血管细胞黏附分子-1 水平显著下降，而依维莫司+MMF 组的 C 反应蛋白、血管细胞黏附分子-1 和血管性血友病因子水平显著升高。
结论
转换为依维莫司和减少 CNI 并不影响维持性 HTx 受者的 CAV 进展。然而，背景免疫抑制治疗很重要，因为依维莫司+AZA 组患者的 CAV 进展和炎症标志物水平下降，而依维莫司+MMF 组则相反。依维莫司与 AZA 联合使用时与 MMF 联合使用的效果不同，这可能反映了目前尚不清楚的相互作用。
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