G-CSF's Last Stand in STEMI.
G-CSF's Last Stand in STEMI.
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G-CSF 在 STEMI 中的最后一站。
DOI：
10.1161/circresaha.119.315454
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发表时间：
2019
影响因子：
20.1
通讯作者：
Traverse,JayH
中科院分区：
文献类型：
--
作者：
Traverse,JayH
308 Circulation Research 2019年7月19日与对照组相比，6个月时G-CSF剂量与较低的不良重塑（LV舒张末期容积）和梗死面积相关。11与之前许多关于G-CSF在STEMI中的阴性研究相反，作者在经皮冠状动脉介入再灌注12小时内给予高剂量G-CSF，并且仅包括高危患者（左心室射血分数< 45%的前STEMI）-在几项试验中已知对细胞治疗有更好反应的亚组。12在这项迄今为止规模最大的G-CSF STEMI试验中，作者随机分配了161名患者，其中119名受试者（61名G-CSF和58名标准治疗）在基线和6个月时进行了配对心脏MRI。值得注意的是，在有利于对照组的重要指标中存在显著的不平衡，包括缺血时间（5.8 vs 4.3小时）、梗死面积（31.7 vs 25.9 g）和微血管阻塞（41% vs 29%）。在未校正的单变量分析中，与对照组相比，G-CSF仅显著改善LV射血分数（+ 4%）。由于两组之间存在许多基线临床和MRI不平衡，因此需要进行多变量分析以揭示G-CSF的重要治疗差异，包括改善心肌应变、缩小梗死面积和通过较小的LV收缩末期容积减轻重塑。然而，该试验与10年前进行的小型II期试验在左心室舒张末期容积和左心室射血分数变化方面的不同结果提醒人们，尽管患者人群几乎相同，但小型临床试验中可能发生不一致。
308 Circulation Research July 19, 2019 dose of G-CSF was associated with lower adverse remodeling (LV end-diastolic volume) and infarct size compared with control at 6 months. 11 In contrast to the many previous negative studies of G-CSF in STEMI, the authors administered high-dose G-CSF within 12 hours of reperfusion with percutaneous coronary intervention and included only high-risk patients (anterior STEMI with LV ejection fraction< 45%)—a subgroup known to have a better response to cell therapy in several trials. 12In this, the largest G-CSF STEMI trial to date, the authors randomized 161 patients of whom 119 subjects (61 G-CSF and 58 standard of care) had paired cardiac MRIs at baseline and 6 months. Notable was the significant imbalance in important metrics that favored the control group including ischemic time (5.8 versus 4.3 hours), infarct size (31.7 versus 25.9 g), and microvascular obstruction (41% versus 29%). Only LV ejection fraction was significantly improved by G-CSF (+ 4%) compared with control in the unadjusted univariable analysis. Because of the many baseline clinical and MRI imbalances between the groups, important treatment differences required multivariable analysis to reveal benefits of G-CSF that included improved myocardial strain, reduction in infarct size, and attenuated remodeling through a smaller LV end-systolic volume. However, the disparate findings between this trial and their smaller phase 2 trial conducted 10 years earlier in regard to changes in LV end-diastolic volume and LV ejection fraction stands out as a reminder of the inconsistencies that may occur in small clinical trials despite having a nearly identical patient population.