The Evolution of Antiplatelet Therapy in the Treatment of Acute Coronary Syndromes
The Evolution of Antiplatelet Therapy in the Treatment of Acute Coronary Syndromes
复制标题
抗血小板治疗在急性冠脉综合征治疗中的进展
作者：
D. Angiolillo
在过去的40年里，我们对血小板介导的血栓形成机制的了解有了显著的增长。通过针对血小板活化和聚集过程的关键介质，这一认识的增加确定了急性冠脉综合征(ACS)的治疗策略。阿司匹林(乙酰水杨酸)单一疗法通过不可逆转地抑制花生四烯酸途径中的环氧合酶(COX)-1酶来改善患者的预后。后来开发的硫代吡啶类前药不可逆转地抑制了P2Y12受体，从而与二磷酸腺苷(ADP)结合，进一步加强了对血小板的抑制和患者的预后。硫代吡啶氯吡格雷已经成为治疗的标准，但它受到可变反应和治疗失败的限制。一种更有效的硫代吡啶，普拉格雷，需要较少的肝脏代谢步骤才能激活，并显著改善了ACS患者的预后。与氯吡格雷相比，普拉格雷的药效增强与心肌梗死(TIMI)定义的大出血的溶栓增加有关。替卡格雷代表了一种新的化学类别的药物，称为环戊基三唑嘧啶。它与血小板的P2Y12受体可逆地相互作用，不需要代谢生物激活就能发挥作用。数据显示，与氯吡格雷相比，替卡格雷在包括死亡率在内的缺血结局方面有显著改善，总体大出血没有增加，尽管非冠状动脉旁路移植出血增加了。糖蛋白IIb/IIIa靶向制剂(阿昔单抗、替罗非班和依替菲肽)也用于接受经皮冠状动脉介入治疗的急性冠脉综合征患者。这些抑制剂通过阻止纤维蛋白原介导的血小板聚集，利用不同的作用机制。其他抑制血小板的治疗策略正在评估中，包括研究中的蛋白酶激活受体(PAR)-1和血栓素A2拮抗剂。这篇综述着重介绍了这些药物的作用机制，以及ACS治疗的持续进展。
Our knowledge of the mechanisms of platelet-mediated thrombosis has increased dramatically over the last 40 years. This increased understanding has identified treatment strategies for acute coronary syndromes (ACS) by targeting key mediators of platelet activation and aggregation processes. Aspirin (acetylsalicylic acid) monotherapy improves patient outcomes by irreversibly inhibiting the cyclooxygenase (COX)-1 enzyme in the arachidonic acid pathway. The later-developed thienopyridines, prodrugs that irreversibly inhibit the P2Y12 receptor, and therefore adenosine diphosphate (ADP) binding, further enhance platelet inhibition and patient outcomes. The thienopyridine clopidogrel has been the standard of care, but it is limited by variable response and treatment failure. A more potent thienopyridine, prasugrel, requires fewer hepatic metabolic steps for activation, and elicits significantly improved outcomes for patients with ACS. The increased potency of prasugrel is associated with an increase in Thrombolysis in Myocardial Infarction (TIMI)-defined major bleeding compared with clopidogrel. Ticagrelor represents a new chemical class of agents called the cyclopentyltriazolopyrimidines. It interacts reversibly with the platelet P2Y12 receptor, and does not require metabolic bioactivation for activity. Data show a significant improvement in ischaemic outcomes, including mortality, for ticagrelor compared with clopidogrel, without an increase in overall major bleeding, although non-coronary artery bypass graft bleeding is increased. Glycoprotein IIb/IIIa targeted agents (abciximab, tirofiban and eptifibatide) are also used in ACS patients undergoing percutaneous coronary interventions. These inhibitors utilize a different mechanism of action by preventing fibrinogen-mediated platelet aggregation. Other therapeutic strategies for platelet inhibition are being evaluated, including the investigative protease-activated receptor (PAR)-1 and thromboxane A2 antagonists. This review highlights the mechanisms of action of these agents, and the continuing evolution of ACS therapy.
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DOI：
10.1001/jama.2010.1543
发表时间：
2010-10-27
期刊：
JAMA
影响因子：
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