De Luca Giuseppe, Verburg Ashley, Hof Arnoud Van't, Ten Berg Jurrien, Kereiakes Dean J, Coller Barry S, Gibson Charles Michael
Division of Cardiology, Polyclinic G. Martino, University of Messina, 98122 Messina, Italy.
Division of Cardiology, IRCSS Hospital Nuovo-Galeazzi Sant'Ambrogio, 20157 Milan, Italy.
Biomedicines. 2024 Sep 4;12(9):2023. doi: 10.3390/biomedicines12092023.
Acute myocardial infarction still represents the major cause of mortality in high-income countries. Therefore, considerable efforts have been focused on the treatment of myocardial infarctions in the acute and long-term phase, with special attention being paid to reperfusion strategies and adjunctive antithrombotic therapies. In fact, despite the successful mechanical recanalization of the epicardial conduit, a substantial percentage of patients still experience poor myocardial reperfusion or acute/subacute in-stent thrombosis. Due the delayed onset of action of currently available oral antiplatelet therapies, glycoprotein (GP) IIb-IIIa inhibitors could be expected to improve clinical outcomes, especially when administrated in the early phase of the infarction, due to the larger platelet composition of fresh thrombi, the dynamic nature of early thrombi, and the larger amount of viable myocardium existing in the early, as compared to a delayed, phase. Considerable evidence has accumulated regarding the benefits from GP IIb-IIIa inhibitors on mortality, especially among high-risk patients and when administered as an upstream strategy. Therefore, based on currently available data, GP IIb-IIIa inhibitors can be considered when the drug can be administered within the first 3 h of symptom onset and among high-risk patients (e.g., those with advanced Killip class or an anterior myocardial infarction). Even though it is not universally accepted, in our opinion, this strategy should be implemented in a pre-hospital setting (in an ambulance) or as soon as possible when arriving at the hospital (at the Emergency Room or Coronary Care Unit, irrespective of whether they are in spoke or hub hospitals). A new, second-generation GP IIb-IIIa inhibitor (zalunfiban) appears to be highly suitable as a pre-hospital pharmacological facilitation strategy at the time of first medical contact due to its favourable features, including its simple subcutaneous administration, rapid onset of action (15 min), and limited time of action (with a half-life of ~1 h), which is likely to minimize the risk of bleeding. The ongoing CELEBRATE trial, including 2499 STEMI patients, may potentially provide compelling data to support the upstream treatment of STEMI patients undergoing mechanical reperfusion. In fact, although the current therapeutic target of increased rates of timely reperfusion has been achieved, the future goal in myocardial infarction treatment should be to achieve the most rapid reperfusion prior to primary percutaneous coronary intervention, thus further minimizing myocardial damage, or, in some cases, even preventing it completely, and improving survival.
急性心肌梗死仍然是高收入国家的主要死亡原因。因此，人们在急性和长期阶段的心肌梗死治疗方面投入了大量精力，特别关注再灌注策略和辅助抗栓治疗。事实上，尽管心外膜血管成功实现了机械再通，但仍有相当比例的患者心肌再灌注不佳或发生急性/亚急性支架内血栓形成。由于目前可用的口服抗血小板治疗起效延迟，糖蛋白（GP）IIb-IIIa抑制剂有望改善临床结局，特别是在梗死早期给药时，因为新鲜血栓中血小板成分更多、早期血栓具有动态特性，且与延迟期相比，早期存在更多存活心肌。关于GP IIb-IIIa抑制剂对死亡率的益处，尤其是在高危患者中以及作为上游策略给药时，已有大量证据积累。因此，根据现有数据，当药物可在症状发作后3小时内给药且针对高危患者（如Killip分级较高或前壁心肌梗死患者）时，可考虑使用GP IIb-IIIa抑制剂。尽管这一策略尚未被普遍接受，但我们认为，应在院前环境（救护车上）或到达医院后尽快（在急诊室或冠心病监护病房，无论其是基层医院还是中心医院）实施。一种新型第二代GP IIb-IIIa抑制剂（扎伦非班）因其有利特性，似乎非常适合作为首次医疗接触时的院前药理促进策略，这些特性包括简单的皮下给药、快速起效（15分钟）和有限的作用时间（半衰期约1小时），这可能会将出血风险降至最低。正在进行的CELEBRATE试验纳入了2499例ST段抬高型心肌梗死（STEMI）患者，可能会提供有力数据支持对接受机械再灌注的STEMI患者进行上游治疗。事实上，尽管目前提高及时再灌注率的治疗目标已经实现，但心肌梗死治疗的未来目标应该是在进行直接经皮冠状动脉介入治疗之前实现最快的再灌注，从而进一步减少心肌损伤，或在某些情况下甚至完全预防心肌损伤，并提高生存率。
