We studied the translational cardioprotective potential of P2Y₁₂ inhibitors against acute myocardial ischemia/reperfusion injury (IRI) in an animal model of acute myocardial infarction and in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). P2Y₁₂ inhibitors may have pleiotropic effects to induce cardioprotection against acute myocardial IRI beyond their inhibitory effects on platelet aggregation. We compared the cardioprotective effects of clopidogrel, prasugrel, and ticagrelor on infarct size in an in vivo rat model of acute myocardial IRI, and investigated the effects of the P2Y₁₂ inhibitors on enzymatic infarct size (48-h area-under-the-curve (AUC) troponin T release) and clinical outcomes in a retrospective study of STEMI patients from the CONDI-2/ERIC-PPCI trial using propensity score analyses. Loading with ticagrelor in rats reduced infarct size after acute myocardial IRI compared to controls (37 ± 11% vs 52 ± 8%, p < 0.01), whereas clopidogrel and prasugrel did not (50 ± 11%, p > 0.99 and 49 ± 9%, p > 0.99, respectively). Correspondingly, troponin release was reduced in STEMI patients treated with ticagrelor compared to clopidogrel (adjusted 48-h AUC ratio: 0.67, 95% CI 0.47–0.94). Compared to clopidogrel, the composite endpoint of cardiac death or hospitalization for heart failure within 12 months was reduced in STEMI patients loaded with ticagrelor (HR 0.63; 95% CI 0.42–0.94) but not prasugrel (HR 0.84, 95% CI 0.43–1.63), prior to PPCI. Major adverse cardiovascular events did not differ between clopidogrel, ticagrelor, or prasugrel. The cardioprotective effects of ticagrelor in reducing infarct size may contribute to the clinical benefit observed in STEMI patients undergoing PPCI.

我们在急性心肌梗死动物模型和接受初次经皮冠状动脉介入治疗 (PPCI) 的 ST 段抬高心肌梗死 (STEMI) 患者中研究了 P2Y _{12抑制剂对急性心肌缺血/再灌注损伤 (IRI) 的转化心脏保护潜力。}除了对血小板聚集的抑制作用之外， P2Y ₁₂抑制剂可能具有多效性作用，以诱导针对急性心肌 IRI 的心脏保护作用。我们在急性心肌 IRI 大鼠体内模型中比较了氯吡格雷、普拉格雷和替格瑞洛对梗死面积的心脏保护作用，并研究了 P2Y _{12的作用。}使用倾向评分分析对来自 CONDI-2/ERIC-PPCI 试验的 STEMI 患者的回顾性研究中酶促梗死面积（48 小时曲线下面积 (AUC) 肌钙蛋白 T 释放）和临床结果的抑制剂。与对照组相比，在大鼠急性心肌 IRI 后，替格瑞洛负荷减少了梗死面积（37 ± 11% vs 52 ± 8%，p  < 0.01），而氯吡格雷和普拉格雷没有（50 ± 11%，p  > 0.99 和 49 ± 9 ） %, p > 0.99，分别）。相应地，与氯吡格雷相比，接受替格瑞洛治疗的 STEMI 患者的肌钙蛋白释放减少（调整后的 48 小时 AUC 比率：0.67，95% CI 0.47–0.94）。与氯吡格雷相比，服用替格瑞洛（HR 0.63；95% CI 0.42-0.94）但不服用普拉格雷（HR 0.84，95% CI 0.43-1.63）的 STEMI 患者，12 个月内心源性死亡或因心力衰竭住院的复合终点降低)，在 PPCI 之前。主要不良心血管事件在氯吡格雷、替格瑞洛或普拉格雷之间没有差异。替格瑞洛在减少梗死面积方面的心脏保护作用可能有助于在接受 PPCI 的 STEMI 患者中观察到临床益处。