Brenner Christoph, Adrion Christine, Grabmaier Ulrich, Theisen Daniel, von Ziegler Franz, Leber Alexander, Becker Alexander, Sohn Hae-Young, Hoffmann Ellen, Mansmann Ulrich, Steinbeck Gerhard, Franz Wolfgang-Michael, Theiss Hans Diogenes
Department of Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck, Innsbruck, Austria; Department of Internal Medicine I, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Institute for Medical Informatics, Biometry und Epidemiology (IBE), Ludwig-Maximilians-University, Munich, Germany.
Int J Cardiol. 2016 Feb 15;205:23-30. doi: 10.1016/j.ijcard.2015.11.180. Epub 2015 Nov 30.
In animal models, G-CSF based progenitor cell mobilization combined with a DPP4 inhibitor leads to increased homing of bone marrow derived progenitor cells to the injured myocardium via the SDF1/CXCR4 axis resulting in improved ejection fraction and survival after acute myocardial infarction (AMI).
After successful revascularization in AMI, 174 patients were randomized 1:1 in a multi-centre, prospective, placebo-controlled, parallel group, double blind, phase III efficacy and safety trial to treatment with G-CSF and Sitagliptin (GS) or placebo. Diabetic and non-diabetic patients were included in our trial. The primary efficacy endpoint hierarchically combined global left and right ventricular ejection fraction changes from baseline to 6 months of follow-up (ΔLVEF, ΔRVEF), as determined by cardiac MRI.
At follow-up ΔLVEF as well as ΔRVEF did not differ between the GS and placebo group. Patients in the placebo group had a similar risk for a major adverse cardiac event within 12 months of follow-up as compared to patients under GS.
Progenitor cell therapy comprising the use of G-CSF and Sitagliptin after successfully revascularized acute myocardial infarction fails to show a beneficial effect on cardiac function and clinical events after 12 months. (EudraCT: 2007-003,941-34; ClinicalTrials.gov: NCT00650143, funding: Heinz-Nixdorf foundation).
在动物模型中，基于粒细胞集落刺激因子（G-CSF）的祖细胞动员联合二肽基肽酶4（DPP4）抑制剂，可通过基质细胞衍生因子1（SDF1）/CXC趋化因子受体4（CXCR4）轴，增加骨髓来源的祖细胞向受损心肌的归巢，从而改善急性心肌梗死（AMI）后的射血分数和生存率。
在急性心肌梗死成功实现血运重建后，174例患者被随机分为1:1，纳入一项多中心、前瞻性、安慰剂对照、平行组、双盲、III期疗效和安全性试验，接受G-CSF和西他列汀（GS）治疗或安慰剂治疗。我们的试验纳入了糖尿病和非糖尿病患者。主要疗效终点是通过心脏磁共振成像（MRI）测定的，从基线到随访6个月时左、右心室射血分数的总体变化（ΔLVEF、ΔRVEF）的分层组合。
在随访时，GS组和安慰剂组之间的ΔLVEF以及ΔRVEF没有差异。与接受GS治疗的患者相比，安慰剂组患者在随访12个月内发生主要不良心脏事件的风险相似。
在急性心肌梗死成功实现血运重建后，使用G-CSF和西他列汀的祖细胞疗法在12个月后未显示出对心脏功能和临床事件有有益影响。（欧盟临床试验注册号：2007-003,941-34；美国国立医学图书馆临床试验注册中心编号：NCT00650143，资助：海因茨-尼克斯多夫基金会）
