Lhermusier Thibault, Waksman Ron
MedStar Washington Hospital Center, Department of Interventional Cardiology , 110 Irving Street, NW, Suite 4B-1, Washington, DC 20010 , USA +1 202 877 2812 ; +1 202 877 2715 ;
Expert Opin Pharmacother. 2015 Mar;16(4):585-96. doi: 10.1517/14656566.2015.1005602. Epub 2015 Jan 29.
P2Y12 receptor antagonists, by inhibiting platelet activation and subsequent aggregation, are critical to prevent ischemic event recurrence after an acute coronary syndrome (ACS). Prasugrel is a third-generation thienopyridine whose metabolites target the P2Y12 receptor. Compared with clopidogrel, prasugrel has a more potent, faster in onset, and more consistent P2Y12 receptor inhibition.
This review describes prasugrel chemistry, pharmacokinetics, pharmacodynamics and clinical studies. In a Phase III randomized clopidogrel-controlled trial, prasugrel improved cardiovascular outcome (risk reduction of cardiovascular death, non-fatal heart attack and non-fatal stroke) at the cost of increased major and fatal bleeding complications. Prasugrel, in combination with aspirin, has been approved by European and American regulatory agencies for the prevention of atherothrombotic events in patients with ACS who undergo percutaneous coronary intervention (PCI).
Prasugrel is effective for managing ACS patients with planned PCI and it offers an alternative with potential benefits over clopidogrel. Prasugrel is currently challenged by ticagrelor, a P2Y12 receptor antagonist with different pharmacokinetic/pharmacodynamic properties. The superiority of one drug to the other cannot be reliably estimated from the current trials. Ongoing randomized and observational studies may help to provide valuable information on the safety and efficacy of these two drugs and their respective places with ACS patients.
P2Y12受体拮抗剂通过抑制血小板活化及随后的聚集，对于预防急性冠状动脉综合征（ACS）后缺血事件复发至关重要。普拉格雷是第三代噻吩并吡啶类药物，其代谢产物作用于P2Y12受体。与氯吡格雷相比，普拉格雷对P2Y12受体的抑制作用更强、起效更快且更稳定。
本综述描述了普拉格雷的化学性质、药代动力学、药效动力学及临床研究。在一项III期随机对照试验中，以氯吡格雷为对照，普拉格雷改善了心血管结局（降低心血管死亡、非致死性心肌梗死和非致死性卒中的风险），但代价是严重及致死性出血并发症增加。普拉格雷与阿司匹林联合应用已获欧美监管机构批准，用于预防接受经皮冠状动脉介入治疗（PCI）的ACS患者发生动脉粥样硬化血栓形成事件。
普拉格雷对计划行PCI的ACS患者有效，且与氯吡格雷相比有潜在益处。目前普拉格雷受到替格瑞洛的挑战，替格瑞洛是一种具有不同药代动力学/药效动力学特性的P2Y12受体拮抗剂。从目前的试验中无法可靠地评估一种药物相对于另一种药物的优越性。正在进行的随机和观察性研究可能有助于提供有关这两种药物的安全性和有效性及其在ACS患者中各自地位的有价值信息。
