Department of Cardiac Surgery, Medical University of Vienna, Universitätsklinik für Chirurgie, Vienna, Austria.
Transplantation. 2011 Sep 15;92(5):594-600. doi: 10.1097/TP.0b013e3182279133.
The mammalian target of rapamycin inhibitor sirolimus has been associated with an increased incidence of wound-healing complications after de novo heart transplantation. To evaluate the possibility of a similar association for everolimus, we performed a risk-factor analysis to compare the incidence of incision-related wound complications for everolimus with that of other adjunctive drugs.
Safety data from 1009 heart transplant recipients (n=214, receiving azathioprine; n=84, mycophenolate mofetil (MMF); n=711, everolimus) were reviewed in a post hoc analysis from three randomized, multicenter studies-B253 (n=634), A2403 (n=199), and A2411 (n=176)-in which de novo patients received fixed-dose or concentration-controlled everolimus (target trough, 3-8 ng/mL), azathioprine, or MMF with standard- or reduced-exposure cyclosporine A. Incisional complications were analyzed for incidence, type, and severity up to day 90 posttransplant.
Incisional-complication events occurred in 25 (11.7%) azathioprine, six (7.2%) MMF, and 87 (12.3%) everolimus patients. Serious incisional complications were more frequent with everolimus (6.9%) compared with azathioprine (4.2%; P=0.197) or MMF (1.2%; P=0.051). In a univariate analysis, patient sex, body mass index (BMI), and diabetes were associated with incisional complications. Only BMI was significantly associated with incisional complications in the subsequent multivariate analysis, with the odds of an incisional-complication event increasing by 12.9% for every 1 kg/m increase in BMI (P<0.001).
The incidence of incisional complications with everolimus was generally low, although numerically higher compared with MMF. Our analyses provided no strong evidence that everolimus is an independent risk factor for incisional complications. After de novo heart transplantation, patients with a high BMI are at higher risk of incision-related wound complications.
哺乳动物雷帕霉素靶蛋白抑制剂西罗莫司与心脏移植后新发病例的伤口愈合并发症发生率增加有关。为了评估依维莫司是否存在类似的关联，我们进行了风险因素分析，比较了依维莫司与其他辅助药物相关切口并发症的发生率。
对来自三个随机、多中心研究-B253（n=634）、A2403（n=199）和 A2411（n=176）的 1009 例心脏移植受者（n=214 例接受硫唑嘌呤；n=84 例接受霉酚酸酯（MMF）；n=711 例接受依维莫司）的安全性数据进行了事后分析。在这些研究中，新发病例接受固定剂量或浓度控制的依维莫司（目标谷浓度 3-8ng/ml）、硫唑嘌呤或 MMF 与标准或低剂量环孢素 A 联合治疗。在移植后 90 天内，分析切口并发症的发生率、类型和严重程度。
25 例（11.7%）硫唑嘌呤、6 例（7.2%）MMF 和 87 例（12.3%）依维莫司患者发生切口并发症事件。与硫唑嘌呤（4.2%；P=0.197）或 MMF（1.2%；P=0.051）相比，依维莫司患者更易发生严重切口并发症（6.9%）。在单因素分析中，患者性别、体重指数（BMI）和糖尿病与切口并发症相关。仅 BMI 在随后的多变量分析中与切口并发症显著相关，BMI 每增加 1kg/m，切口并发症事件的发生几率增加 12.9%（P<0.001）。
依维莫司的切口并发症发生率总体较低，尽管与 MMF 相比略高。我们的分析没有提供强有力的证据表明依维莫司是切口并发症的独立危险因素。在心脏移植后，BMI 较高的患者发生与切口相关的伤口并发症的风险更高。
