Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Cardiology, University of Lund, Lund, Sweden.
Heart. 2018 Oct;104(19):1593-1599. doi: 10.1136/heartjnl-2017-312774. Epub 2018 Mar 30.
Reperfusion immediately after reopening of the infarct-related artery in ST-segment elevation myocardial infarction (STEMI) may cause myocardial damage in addition to the ischaemic insult (reperfusion injury). The gap junction modulating peptide danegaptide has in animal models reduced this injury. We evaluated the effect of danegaptide on myocardial salvage in patients with STEMI.
In addition to primary percutaneous coronary intervention in STEMI patients with thrombolysis in myocardial infarction flow 0-1, single vessel disease and ischaemia time less than 6 hours, we tested, in a clinical proof-of-concept study, the therapeutic potential of danegaptide at two-dose levels. Primary outcome was myocardial salvage evaluated by cardiac MRI after 3 months.
From November 2013 to August 2015, a total of 585 patients were randomly enrolled in the trial. Imaging criteria were fulfilled for 79 (high dose), 80 (low dose) and 84 (placebo) patients eligible for the per-protocol analysis. Danegaptide did not affect the myocardial salvage index (danegaptide high (63.9±14.9), danegaptide low (65.6±15.6) and control (66.7±11.7), P=0.40), final infarct size (danegaptide high (19.6±11.4 g), danegaptide low (18.6±9.6 g) and control (21.4±15.0 g), P=0.88) or left ventricular ejection fraction (danegaptide high (53.9%±9.5%), danegaptide low (52.7%±10.3%) and control (52.1%±10.9%), P=0.64). There was no difference between groups with regard to clinical outcome.
Administration of danegaptide to patients with STEMI did not improve myocardial salvage.
NCT01977755; Pre-results.
ST 段抬高型心肌梗死（STEMI）患者梗死相关动脉再通后即刻再灌注可能会导致心肌损伤，除了缺血损伤（再灌注损伤）。缝隙连接调节肽达那肽在动物模型中减少了这种损伤。我们评估了达那肽对 STEMI 患者心肌挽救的效果。
在接受 STEMI 患者的直接经皮冠状动脉介入治疗（PCI）的基础上，我们还对接受心肌梗死溶栓治疗血流 0-1、单支血管病变和缺血时间小于 6 小时的患者进行了临床试验，以测试达那肽的两种剂量水平的治疗潜力。主要结局是通过心脏 MRI 在 3 个月后评估心肌挽救。
2013 年 11 月至 2015 年 8 月，共纳入 585 例患者参与该试验。符合影像学标准的患者共有 79 例（高剂量组）、80 例（低剂量组）和 84 例（安慰剂组）可进行意向性治疗分析。达那肽并未影响心肌挽救指数（达那肽高剂量组（63.9±14.9）、达那肽低剂量组（65.6±15.6）和安慰剂组（66.7±11.7），P=0.40）、最终梗死面积（达那肽高剂量组（19.6±11.4g）、达那肽低剂量组（18.6±9.6g）和安慰剂组（21.4±15.0g），P=0.88）或左心室射血分数（达那肽高剂量组（53.9%±9.5%）、达那肽低剂量组（52.7%±10.3%）和安慰剂组（52.1%±10.9%），P=0.64）。各组之间的临床结局没有差异。
在 STEMI 患者中使用达那肽并未改善心肌挽救。
NCT01977755；预试验结果。
