Antiplatelet therapy after percutaneous coronary intervention: Should another regimen be "TAPT?".
Antiplatelet therapy after percutaneous coronary intervention: Should another regimen be "TAPT?".
复制标题
经皮冠状动脉介入治疗后的抗血小板治疗：是否应该另一种治疗方案是“TAPT？”。
DOI：
10.1161/circinterventions.110.936948
复制
发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Croce,Kevin
中科院分区：
文献类型：
--
作者：
Croce,Kevin
经皮冠状动脉介入治疗（PCI）后ADP受体拮抗剂氯吡格雷。这些建议基于以下数据：与阿司匹林或阿司匹林联合华法林相比，P2Y12抑制剂氯吡格雷DAPT可减少稳定型心绞痛和急性冠脉综合征（ACS）患者PCI术后的主要不良心脏事件。1尽管接受了DAPT治疗，但与稳定型心绞痛患者相比，接受PCI的ACS患者复发性缺血事件的风险较高，部分原因是ACS患者的血小板血栓形成活性增加。此外，氯吡格雷对血小板的抑制程度存在相当大的个体间差异，氯吡格雷治疗（低反应性）背景下的高残留血小板活性与PCI后不良心血管（CV）事件相关。氯吡格雷低反应性与多种改变药代动力学的临床和遗传因素有关，糖尿病、充血性心力衰竭（CHF）和肥胖与疗效降低有关。氯吡格雷是一种前体药物，需要通过肝细胞色素P450系统（CYP1A1）转化为活性代谢物，在负荷剂量后，氯吡格雷可能需要长达6小时才能发挥最大作用。降低氯吡格雷活性的遗传多态性导致氯吡格雷的肝脏代谢降低。在接受氯吡格雷治疗的患者中，特定功能降低的CYP2C19等位基因携带者的氯吡格雷转化受损，活性代谢产物水平显著降低，血小板抑制作用减弱，PCI后不良CV事件和支架血栓形成的发生率较高。2 CYP2C19多态性的患病率范围为30%至60%，取决于种族。2，3抑制血小板活性的药物也会降低氯吡格雷的转化率，一些降低血小板功能的质子泵抑制剂（PPI）（如奥美拉唑）会降低氯吡格雷的代谢物水平和通过血小板功能测试测量的疗效。氯吡格雷和PPI之间的相互作用目前存在争议。早期观察性研究表明，服用氯吡格雷和PPI的患者的不良CV事件增加;然而，在随机试验（包括TRITON TIMI-38和COGENT）中对接受氯吡格雷治疗的患者进行的分析表明，PPI使用与不良CV事件风险之间无相关性。4，5这些发现强调了一点，即通过血小板功能检测测量的生物学相互作用可能并不总是预测影响CV结局的临床相互作用。
ADP receptor antagonist clopidogrel after percutaneous coronary intervention (PCI). These recommendations are based on data that DAPT with the P2Y12 inhibitors clopidogrel reduces major adverse cardiac events after PCI in stable angina and acute coronary syndrome (ACS) patients when compared with aspirin, or aspirin in combination with warfarin. 1 Despite treatment with DAPT, patients with ACS undergoing PCI are at elevated risk for recurrent ischemic events compared with stable angina patients in part because of increased platelet thrombotic activity in ACS. In addition, there is considerable interindividual variability in the degree of platelet inhibition achieved by clopidogrel, and high residual platelet activity in the setting of clopidogrel therapy (hyporesponsiveness) is associated with adverse cardiovascular (CV) events after PCI. Clopidogrel hyporesponsiveness is related to a variety of clinical and genetic factors that alter pharmacokinetics, and diabetes, congestive heart failure (CHF), and obesity are associated with reduced efficacy. Clopidogrel is a prodrug that requires conversion by the hepatic cytochrome P450 system (CYP) to an active metabolite, and it can take up to 6 hours for clopidogrel to have maximal effect after the loading dose. Genetic polymorphisms that reduce CYP activity result in decreased hepatic metabolism of clopidogrel. Among persons treated with clopidogrel, carriers of specific reduced function CYP2C19 alleles have impaired clopidogrel conversion, significantly lower levels of active metabolite, diminished platelet inhibition, and higher rates of adverse CV events and stent thrombosis after PCI. 2 The prevalence of CYP2C19 polymorphisms ranges from 30% to 60% depending on ethnicity. 2, 3 Medications that inhibit CYP activity also reduce clopidogrel conversion, and some proton pump inhibitors (PPI) that reduce CYP function (eg, omeprazole) diminish clopidogrel metabolite levels and efficacy measured by platelet function testing. The interaction between clopidogrel andPPIs is currently controversial. Early observational studies suggested increased adverse CV events in patients taking clopidogrel and a PPI; however, analysis of patients treated with clopidogrel in randomized trials including TRITON TIMI-38 and COGENT demonstrated no association between PPI use and risk of adverse CV events. 4, 5 These findings highlight the point that biological interaction measured with platelet function testing may not always predict clinical interactions that affect CV outcomes.