The Quest for the Optimal Periprocedural Antithrombotic Treatment Strategy in ACS Patients Undergoing PCI.
The Quest for the Optimal Periprocedural Antithrombotic Treatment Strategy in ACS Patients Undergoing PCI.
复制标题
寻求接受 PCI 的 ACS 患者的最佳围手术期抗血栓治疗策略。
DOI：
10.1016/j.jacc.2018.01.040
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发表时间：
2018
影响因子：
24
通讯作者：
Franchi,Francesco
中科院分区：
文献类型：
--
作者：
Angiolillo,DominickJ;Rollini,Fabiana;Franchi,Francesco
急性冠状动脉综合征（ACS）的早期特征是血栓性并发症的风险增加，强调需要快速、安全和有效的抗血栓治疗，特别是在接受经皮冠状动脉介入治疗（PCI）的患者中（1，2）。由于凝血酶在增强血栓形成前环境中的核心作用，因此在这种情况下，靶向凝血酶介导作用的策略变得至关重要（1，2）。在这种程度上，普通肝素（UFH）和比伐卢定是临床实践中可用的速效静脉抗凝剂。UFH是一种间接凝血酶和Xa因子抑制剂，其药代动力学和药效学特征表现为患者内和患者间变异性高（2）。此外，UFH与血小板反应性增加有关（3）。在引入更有效的口服P2 Y12抑制剂之前，糖蛋白IIb/IIIa抑制剂（GPIs）通常用于UFH的辅助治疗，以减少围手术期血栓形成事件。然而，使用GPI后严重出血并发症的发生率增加，以及对出血相关不良预后影响（包括死亡率增加）的认识不断提高，加强了减少出血策略的重要性（4，（五）。比伐卢定是一种直接凝血酶抑制剂，具有线性剂量-效应曲线，可产生更可预测的抗凝作用（2）。多项临床试验支持在接受PCI的ACS患者中，比伐卢定与UFH联合常规静脉注射GPIs相比具有上级的安全性（即减少出血），且疗效无折衷（6）。然而，技术专长和设备的发展，以及接受PCI的患者可用的抗血栓治疗设备的扩展，导致GPI使用的下降（4）。这不可避免地质疑了比伐卢定在现代介入药理学中的作用，其主要特征是仅临时使用GPI。在此背景下，在MATRIX（通过经桡动脉穿刺部位和全身实施Angiox最大限度地减少不良出血事件）试验中，接受PCI的ACS患者随机接受比伐卢定或UFH（伴或不伴GPIs），由术者决定。MATRIX试验旨在证明比伐卢定在30天时的主要不良心血管事件（MACE;死亡、心肌梗死或卒中的复合事件）和净不良临床事件（NACE;与冠状动脉旁路移植术无关的MACE或大出血的复合事件）（出血学术研究联盟[BARC] 3或5型）的共同主要终点方面优于UFH GPI。然而，尽管大出血、全因死亡和心源性死亡显著减少，但两项主要终点均未达到（7）。
The early phase of an acute coronary syndrome (ACS) is characterized by an increased risk of thrombotic complications, underscoring the need for fast-acting, safe, and efficacious antithrombotic therapies, particularly among patients undergoing percutaneous coronary intervention (PCI)(1, 2). Because of the central role of thrombin on enhancing the prothrombotic milieu, strategies that target thrombin-mediated effects have become essential in this setting (1, 2). To this extent, unfractionated heparin (UFH) and bivalirudin are fast-acting intravenous anticoagulants available in clinical practice. UFH is an indirect thrombin and factor Xa inhibitor, the pharmacokinetic and pharmacodynamic profiles of which are characterized by high intra-and interpatient variability (2). Moreover, UFH has been associated with an increase in platelet reactivity (3). Before the introduction of the more effective oral P2Y12 inhibitors, glycoprotein IIb/IIIa inhibitors (GPIs) were commonly used in adjunct to UFH to reduce periprocedural thrombotic events.However, the increased rates of major bleeding complications with GPI use and the ever-increasing awareness of the poor prognostic implications associated with bleeding, including increased mortality, have reinforced the importance of bleeding reduction strategies (4, 5). Bivalirudin is a direct thrombin inhibitor with a linear doseÀresponse profile that leads to more predictable anticoagulant effects (2). Several clinical trials have supported the superior safety (ie, reduced bleeding), without a tradeoff in efficacy, of bivalirudin compared with UFH plus routinely administered intravenous GPIs in ACS patients who are undergoing PCI (6). However, the evolution in technical expertise and devices, as well as the expansion of the armamentarium of antithrombotic therapies available for patients undergoing PCI, have led to a decline in GPI use (4). This has inevitably questioned the role of bivalirudin in the modern era of interventional pharmacology, which is largely characterized by only provisional GPI use. With this background, in the MATRIX (Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial, patients with an ACS who underwent PCI were randomized to receive either bivalirudin or UFH with or without GPIs at operator discretion. The MATRIX trial was designed to demonstrate the superiority of bivalirudin over UFH Æ GPI on the coprimary endpoints of major adverse cardiovascular events (MACEs; a composite of death, myocardial infarction, or stroke) and net adverse clinical events (NACEs; a composite of MACEs or major bleeding not related to coronary artery bypass graft)(Bleeding Academic Research Consortium [BARC] type 3 or 5) at 30 days. However, despite a significant reduction in major bleeding, all-cause death, and cardiac death, neither of the primary endpoints were met (7).