JAMA:骨髓单核细胞移植治疗未能改善心肌梗死后结局
2011-12-08 MedSci原创 MedSci原创
奥兰多(EGMN)——美国心脏学会年会上公布的一项前瞻性随机对照研究显示，在初次心肌梗死(MI)后2~3周进行冠状动脉内输注骨髓细胞(BMC)是安全的，但随访6个月发现全身或局部功能无明显改善(JAMA 2011 Nov. 14 [doi: doi:10.1001/jama.2011.1670])。但这一报道与REPAIR-AMI:干细胞治疗心肌梗死5年后仍有
奥兰多(EGMN)——美国心脏学会年会上公布的一项前瞻性随机对照研究显示，在初次心肌梗死(MI)后2~3周进行冠状动脉内输注骨髓细胞(BMC)是安全的，但随访6个月发现全身或局部功能无明显改善(JAMA 2011 Nov. 14 [doi: doi:10.1001/jama.2011.1670])。但这一报道与REPAIR-AMI:干细胞治疗心肌梗死5年后仍有收益呈现相反的结果.
这项最新研究由雅培西北医院明尼阿波利斯心脏研究所的Jay Traverse博士及其同事进行，共纳入87例患者，患者被分成BMC组(n=58)和安慰剂组(n=29)，这两组患者分别在初次经皮介入治疗后 17.4 d(中位数)和16.8 d(中位数)接受骨髓穿刺和冠状动脉内输注150×106总有核细胞。研究者认为，如果患者起初的病情过重或者就诊的医院不具备开展细胞治疗的能力，则稍晚进行输注可能尤为重要。
该高危队列罹患的主要是大面积前壁MI，BMC组和安慰剂组的平均左心室射血分数(LVEF)分别为36.4%和35%，平均肌酸激酶MB分数峰值分别为234和318。2/3的患者置入药物洗脱支架，半数以上为吸烟者或患有高脂血症。
随访6个月的结果显示，BMC组的LVEF仅增加0.5%(从48.7%增至49.2%)，而安慰剂组增加3.5%(从45.3%增至48.8%)，组间增幅差异不显著(P=0.14)。在81例可评价患者中观察到的室壁运动变化(共同主要终点)相似。BMC组梗死区的室壁运动从平均6.2 mm增至6.5 mm，安慰剂组从4.9 mm增至5.9 mm。BMC组边缘区室壁运动从平均16 mm增至16.6 mm，安慰剂组从16.1 mm增至19.3 mm。两组的梗死面积和左心室容积的变化相似。安慰剂组1例患者死亡，BMC组1例患者复发MI。安慰剂组和BMC组分别有3例和1例患者需再次进行血运重建。安慰剂组2例患者需置入心律转复除颤器，BMC组1例患者因心力衰竭住院。BMC组的总事件发生率显著低于安慰剂组(5% vs. 17%)。
汉堡实验药理学与毒理学研究所的Thomas Eschenhagen博士评论指出，2006年开展的一些早期研究表明，在临床上通过对患者输注自体骨髓单个核细胞来提高心脏功能是可行、安全且有效的。疗效的预测因子包括低射血分数和相对较晚输注BMC(MI后5~7 d)。本项研究未观察到BMC疗效，可能是因为在经皮介入治疗后2周以上才进行输注。此外，该研究仅纳入87例患者，样本量较小，而且未在动物模型中检测细胞的效率。Eschenhagen博士对包括本项研究在内的11项BMC研究进行粗略计算发现，左室功能平均加权增加率仅为0.43%。这些BMC研究的中性结果表明，BMC对急性或亚急性MI的疗效仍存争议。
该研究获美国心肺血液研究所资助。Traverse博士无有关经济利益冲突的声明，1位研究者声明是Juventas Therapeutics和Aastrom Biosciences公司的顾问，并从Athersys公司获得资助。
原始文献:
Abstract
Context Clinical trial results suggest that intracoronary delivery of autologous bone marrow mononuclear cells (BMCs) may improve left ventricular (LV) function when administered within the first week following myocardial infarction (MI). However, because a substantial number of patients may not present for early cell delivery, the efficacy of autologous BMC delivery 2 to 3 weeks post-MI warrants investigation.
Objective To determine if intracoronary delivery of autologous BMCs improves global and regional LV function when delivered 2 to 3 weeks following first MI.
Design, Setting, and Patients A randomized, double-blind, placebo-controlled trial (LateTIME) of the National Heart, Lung, and Blood Institute–sponsored Cardiovascular Cell Therapy Research Network of 87 patients with significant LV dysfunction (LV ejection fraction [LVEF] ≤45%) following successful primary percutaneous coronary intervention (PCI) between July 8, 2008, and February 28, 2011.
Interventions Intracoronary infusion of 150 × 106 autologous BMCs (total nucleated cells) or placebo (BMC:placebo, 2:1) was performed within 12 hours of bone marrow aspiration after local automated cell processing.
Main Outcome Measures Changes in global (LVEF) and regional (wall motion) LV function in the infarct and border zone between baseline and 6 months, measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volumes and infarct size.
Results A total of 87 patients were randomized (mean [SD] age, 57 [11] years; 83% men). Harvesting, processing, and intracoronary delivery of BMCs in this setting was feasible. Change between baseline and 6 months in the BMC group vs placebo for mean LVEF (48.7% to 49.2% vs 45.3% to 48.8%; between-group mean difference, −3.00; 95% CI, −7.05 to 0.95), wall motion in the infarct zone (6.2 to 6.5 mm vs 4.9 to 5.9 mm; between-group mean difference, −0.70; 95% CI, −2.78 to 1.34), and wall motion in the border zone (16.0 to 16.6 mm vs 16.1 to 19.3 mm; between-group mean difference, −2.60; 95% CI, −6.03 to 0.77) were not statistically significant. No significant change in LV volumes and infarct volumes was observed; both groups decreased by a similar amount at 6 months vs baseline.
Conclusion Among patients with MI and LV dysfunction following reperfusion with PCI, intracoronary infusion of autologous BMCs vs intracoronary placebo infusion, 2 to 3 weeks after PCI, did not improve global or regional function at 6 months.
Trial Registration clinicaltrials.gov Identifier: NCT00684060
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#细胞移植#
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#单核细胞#
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