Steinhubl Steven, Roe Matthew T
Gill Heart Institute, University of Kentucky, Lexington, Kentucky 40536, USA.
Cardiovasc Drug Rev. 2007 Summer;25(2):188-203. doi: 10.1111/j.1527-3466.2007.00013.x.
Guidelines recommend that dual antiplatelet therapy using aspirin and clopidogrel should be administered to the majority of patients with acute coronary syndromes, including those undergoing percutaneous coronary intervention (PCI). However, the results of a large randomized, placebo-controlled study suggest that a 300-mg loading dose of clopidogrel must be administered at least 15 h prior to PCI in order to achieve a significant reduction in peri-PCI thrombotic events. Other data suggest that 2 h of pretreatment may be sufficient if a 600-mg loading dose is used. Since it is often difficult to achieve an adequate pretreatment goal with clopidogrel in clinical practice, more rapid achievement of platelet P2Y(12) inhibition may improve patient outcomes. Prasugrel, [6-[2-(3,4-diflurophenyl) cyclopropyl1-1-y1] amino-2-propylthio-9-D-ribofuranosyl-9H-purine (AZD6140), and cangrelor are platelet P2Y(12) receptor antagonists currently in development that offer faster acting inhibition of adenosine diphosphate (ADP)--induced platelet aggregation. These agents act upon the same platelet receptor as clopidogrel, but are distinguished by their routes of administration, reversibility, and pharmacodynamic properties. Prasugrel is an orally administered agent that provides faster, higher, and more consistent inhibition of platelet aggregation than clopidogrel. The results of Phase II testing suggest that the risk of bleeding is similar in prasugrel- and clopidogrel-treated patients. AZD6140 is another orally administered platelet inhibitor with rapid and reversible action. Again, Phase II testing suggests similar bleeding risk for clopidogrel. Preliminary evidence suggests that clinical outcomes may be better in prasugrel- and AZD6140-treated patients than in clopidogrel-treated patients. Cangrelor is an intravenously administered, reversible, short-acting agent with a rapid onset of activity. Bleeding risk and clinical outcomes data are similar in cangrelor- and abciximab-treated patients. The results of ongoing Phase III clinical trials involving more than 40,000 patients will demonstrate whether these agents fulfill their potential to improve outcomes in PCI-treated patients by providing faster, higher, and more consistent inhibition of platelet aggregation.
指南推荐，对于大多数急性冠脉综合征患者，包括接受经皮冠状动脉介入治疗（PCI）的患者，应给予阿司匹林和氯吡格雷双重抗血小板治疗。然而，一项大型随机、安慰剂对照研究的结果表明，为了显著降低PCI围手术期血栓形成事件，氯吡格雷300mg负荷剂量必须在PCI至少15小时前给药。其他数据表明，如果使用600mg负荷剂量，2小时的预处理可能就足够了。由于在临床实践中使用氯吡格雷往往难以实现充分的预处理目标，更快地实现血小板P2Y（12）抑制可能会改善患者预后。普拉格雷、[6-[2-（3,4-二氟苯基）环丙基1-1-y1]氨基-2-丙硫基-9-D-呋喃核糖基-9H-嘌呤（AZD6140）和坎格雷洛是目前正在研发的血小板P2Y（12）受体拮抗剂，它们能更快地抑制二磷酸腺苷（ADP）诱导的血小板聚集。这些药物作用于与氯吡格雷相同的血小板受体，但在给药途径、可逆性和药效学特性方面有所不同。普拉格雷是一种口服药物，与氯吡格雷相比，它能更快、更高且更持续地抑制血小板聚集。II期试验结果表明，接受普拉格雷和氯吡格雷治疗的患者出血风险相似。AZD6140是另一种具有快速和可逆作用的口服血小板抑制剂。同样，II期试验表明其与氯吡格雷的出血风险相似。初步证据表明，接受普拉格雷和AZD6140治疗的患者的临床结局可能优于接受氯吡格雷治疗的患者。坎格雷洛是一种静脉给药、可逆、短效的药物，起效迅速。接受坎格雷洛和阿昔单抗治疗的患者出血风险和临床结局数据相似。涉及40000多名患者的正在进行的III期临床试验结果将证明，这些药物是否通过更快、更高且更持续地抑制血小板聚集来实现其改善PCI治疗患者结局的潜力。
