University of New Mexico College of Pharmacy, Albuquerque, NM 87131-0001, USA.
Cardiol Rev. 2011 Mar-Apr;19(2):95-100. doi: 10.1097/CRD.0b013e3182099d86.
The complex mechanism of platelet activation creates an optimal target for pharmacological treatment in patients with acute coronary syndromes. Current antiplatelet medications that are used in addition to aspirin include the thienopyridines, clopidogrel and prasugrel, but there are several limitations to the use of these medications. Clopidogrel and prasugrel irreversibly bind to the P2Y12 receptor, creating a prolonged antiplatelet effect which can be undesirable when surgery is needed. Clopidogrel requires hepatic activation and produces variable platelet inhibition based on genetic polymorphisms. Prasugrel has more consistent platelet inhibition than clopidogrel but carries with it an increased risk of serious bleeds. Ticagrelor is a drug in a new chemical class that reversibly binds the P2Y12 receptor and noncompetitively blocks adenosine diphosphate-induced platelet activation. It was specifically designed to address the limitations of the available antiplatelet agents while maintaining comparable or better antiplatelet effects. It does not require metabolic activation and demonstrates greater platelet inhibition, a faster offset of action and comparable bleeding risk compared to clopidogrel. The pivotal PLATO (The Study of Platelet Inhibition and Patient Outcomes) trial in patients with an acute coronary syndrome demonstrated improved cardiovascular outcomes, including a reduction in myocardial infarctions and vascular events using ticagrelor as compared to clopidogrel with comparable rates of major bleeds. A puzzling finding from that trial was the lack of benefit with ticagrelor in patients enrolled from the United States, which has led to ticagrelor not being approved at this time in this country. The main adverse events with ticagrelor are bleeding and dyspnea, the latter of which is of unclear etiology and of unknown long-term clinical concern. In summary, ticagrelor is an exciting new oral antiplatelet drug that seems to be more efficacious than clopidogrel, with comparable safety. Whether issues of geographic disparities in response and the unusual side effect of dyspnea ultimately prove problematic has yet to be determined. Nonetheless, ticagrelor is a drug that has the potential to change the standard of care of patients with acute coronary syndromes.
血小板激活的复杂机制为急性冠状动脉综合征患者的药物治疗创造了一个理想的靶点。除了阿司匹林，目前用于抗血小板的药物还包括噻吩吡啶类、氯吡格雷和普拉格雷，但这些药物的应用存在一些局限性。氯吡格雷和普拉格雷不可逆地结合到 P2Y12 受体上，从而产生持久的抗血小板作用，在需要手术时可能不理想。氯吡格雷需要肝脏激活，并根据遗传多态性产生可变的血小板抑制。普拉格雷比氯吡格雷有更一致的血小板抑制作用，但出血风险增加。替格瑞洛是一种新型化学类药物，可逆地结合 P2Y12 受体，并非竞争性地阻断二磷酸腺苷诱导的血小板激活。它是专门设计用来解决现有抗血小板药物的局限性，同时保持可比或更好的抗血小板作用。它不需要代谢激活，与氯吡格雷相比，显示出更强的血小板抑制作用、更快的作用消除和可比的出血风险。在急性冠状动脉综合征患者中进行的关键 PLATO（血小板抑制和患者结局研究）试验表明，与氯吡格雷相比，使用替格瑞洛可改善心血管结局，包括减少心肌梗死和血管事件，而大出血的主要发生率相似。该试验的一个令人费解的发现是，来自美国的患者使用替格瑞洛没有获益，这导致目前在美国尚未批准使用替格瑞洛。替格瑞洛的主要不良事件是出血和呼吸困难，后者的病因尚不清楚，长期临床关注也不清楚。总之，替格瑞洛是一种令人兴奋的新型口服抗血小板药物，似乎比氯吡格雷更有效，安全性相当。反应的地理差异问题和呼吸困难这一不寻常的副作用最终是否会成为问题，还有待确定。尽管如此，替格瑞洛是一种有可能改变急性冠状动脉综合征患者治疗标准的药物。
