Mangano Dennis T, Miao Yinghui, Tudor Iulia C, Dietzel Cynthia
Ischemia Research and Education Foundation (IREF), San Bruno, California 94066, USA.
J Am Coll Cardiol. 2006 Jul 4;48(1):206-14. doi: 10.1016/j.jacc.2006.04.044. Epub 2006 May 11.
The purpose of this study was to assess the safety and efficacy of the adenosine regulating agent (ARA) acadesine for reducing long-term mortality among patients with post-reperfusion myocardial infarction (MI).
No prospectively applied therapy exists that improves long-term survival after MI associated with coronary artery bypass graft (CABG) surgery-a robust model of ischemia/reperfusion injury. Pretreatment with the purine nucleoside autocoid adenosine mitigates the extent of post-ischemic reperfusion injury in animal models. Therefore, we questioned whether use of the ARA acadesine-by increasing interstitial adenosine concentrations in ischemic tissue-would improve long-term survival after post-reperfusion MI.
At 54 institutions, 2,698 patients undergoing CABG surgery were randomized to receive placebo (n = 1,346) or acadesine (n = 1,352) by intravenous infusion (0.1 mg/kg/min; 7 h) and in cardioplegia solution (placebo or acadesine; 5 microg/ml). Myocardial infarction was prospectively defined as: 1) new Q-wave and MB isoform of creatine kinase (CK-MB) elevation (daily electrocardiography; 16 serial CK-MB measurements); or 2) autopsy evidence. Vital status was assessed over 2 years, and outcomes were adjudicated centrally.
Perioperative MI occurred in 100 patients (3.7%), conferring a 4.2-fold increase in 2-year mortality (p < 0.001) compared with those not suffering MI. Acadesine treatment, however, reduced that mortality by 4.3-fold, from 27.8% (15 of 54; placebo) to 6.5% (3 of 46; acadesine) (p = 0.006), with the principal benefit occurring over the first 30 days after MI. The acadesine benefit was similar among diverse subsets, and multivariable analysis confirmed these findings.
Acadesine is the first therapy proven to be effective for reducing the severity of acute post-reperfusion MI, substantially reducing the risk of dying over the 2 years after infarction.
本研究旨在评估腺苷调节剂阿卡地辛对降低再灌注后心肌梗死（MI）患者长期死亡率的安全性和有效性。
对于与冠状动脉搭桥术（CABG）相关的心肌梗死后改善长期生存，目前尚无前瞻性应用的治疗方法——这是一种强大的缺血/再灌注损伤模型。嘌呤核苷自体活性物质腺苷预处理可减轻动物模型中缺血后再灌注损伤的程度。因此，我们质疑使用阿卡地辛——通过增加缺血组织中的间质腺苷浓度——是否会改善再灌注后心肌梗死后的长期生存。
在54个机构中，2698例接受CABG手术的患者被随机分为接受安慰剂（n = 1346）或阿卡地辛（n = 1352）静脉输注（0.1 mg/kg/min；7小时）以及心脏停搏液（安慰剂或阿卡地辛；5μg/ml）。心肌梗死被前瞻性定义为：1）新的Q波和肌酸激酶（CK-MB）同工酶MB升高（每日心电图检查；16次连续CK-MB测量）；或2）尸检证据。对生命状态进行了2年的评估，结果由中心判定。
围手术期心肌梗死发生在100例患者（3.7%）中，与未发生心肌梗死的患者相比，2年死亡率增加了4.2倍（p < 0.001）。然而，阿卡地辛治疗将死亡率降低了4.3倍，从27.8%（54例中的15例；安慰剂）降至6.5%（46例中的3例；阿卡地辛）（p = 0.006），主要益处出现在心肌梗死后的前30天。阿卡地辛的益处在不同亚组中相似，多变量分析证实了这些发现。
阿卡地辛是第一种被证明对降低急性再灌注后心肌梗死严重程度有效的治疗方法，可大幅降低梗死后2年内死亡的风险。
Zotero 插件