Atar Dan, Petzelbauer Peter, Schwitter Jürg, Huber Kurt, Rensing Benno, Kasprzak Jaroslaw D, Butter Christian, Grip Lars, Hansen Peter R, Süselbeck Tim, Clemmensen Peter M, Marin-Galiano Marcos, Geudelin Bernard, Buser Peter T
Division of Cardiology and Faculty of Medicine, Aker University Hospital, University of Oslo, Oslo, Norway.
J Am Coll Cardiol. 2009 Feb 24;53(8):720-9. doi: 10.1016/j.jacc.2008.12.017.
The purpose of this study was to investigate whether FX06 would limit infarct size when given as an adjunct to percutaneous coronary intervention.
FX06, a naturally occurring peptide derived from human fibrin, has been shown to reduce myocardial infarct size in animal models by mitigating reperfusion injury.
In all, 234 patients presenting with acute ST-segment elevation myocardial infarction were randomized in 26 centers. FX06 or matching placebo was given as intravenous bolus at reperfusion. Infarct size was assessed 5 days after myocardial infarction by late gadolinium enhanced cardiac magnetic resonance imaging. Secondary outcomes included size of necrotic core zone and microvascular obstruction at 5 days, infarct size at 4 months, left ventricular function, troponin I levels, and safety.
There were no baseline differences between groups. On day 5, there was no significant difference in total late gadolinium enhanced zone in the FX06 group compared with placebo (reduction by 21%; p = 0.207). The necrotic core zone, however, was significantly reduced by 58% (median 1.77 g [interquartile range 0.0, 9.09 g] vs. 4.20 g [interquartile range 0.3, 9.93 g]; p < 0.025). There were no significant differences in troponin I levels (at 48 h, -17% in the FX06 group). After 4 months, there were no longer significant differences in scar size. There were numerically fewer serious cardiac events in the FX06-treated group, and no differences in adverse events.
In this proof-of-concept trial, FX06 reduced the necrotic core zone as one measure of infarct size on magnetic resonance imaging, while total late enhancement was not significantly different between groups. The drug appears safe and well tolerated. (Efficacy of FX06 in the Prevention of Myocardial Reperfusion Injury [F.I.R.E.]; NCT00326976).
本研究旨在探讨在经皮冠状动脉介入治疗中加用FX06是否会限制梗死面积。
FX06是一种源自人纤维蛋白的天然肽，已证实在动物模型中可通过减轻再灌注损伤来缩小心肌梗死面积。
总共234例急性ST段抬高型心肌梗死患者在26个中心进行随机分组。在再灌注时静脉推注FX06或匹配的安慰剂。心肌梗死后5天通过延迟钆增强心脏磁共振成像评估梗死面积。次要结局包括5天时坏死核心区大小和微血管阻塞情况、4个月时梗死面积、左心室功能、肌钙蛋白I水平及安全性。
两组间基线无差异。在第5天，FX06组与安慰剂组相比，延迟钆增强总面积无显著差异（减少21%；p = 0.207）。然而，坏死核心区显著减少了58%（中位数1.77 g[四分位间距0.0，9.09 g]对比4.20 g[四分位间距0.3，9.93 g]；p < 0.025）。肌钙蛋白I水平无显著差异（48小时时，FX06组降低17%）。4个月后，瘢痕大小不再有显著差异。FX06治疗组严重心脏事件在数值上较少，不良事件无差异。
在这项概念验证试验中，FX06减少了坏死核心区，这是磁共振成像上梗死面积的一项指标，而两组间延迟增强总量无显著差异。该药物似乎安全且耐受性良好。（FX06预防心肌再灌注损伤的疗效[F.I.R.E.]；NCT00326976）
