CYP2C19抑制效力小的泮托拉唑，从而最大程度地减少药物不良反应和心血管不良事件
的发生；
氯吡格雷与PPI的多代谢途径，不能简单禁止氯吡格雷与PPI联用； 药理理论研究不能完全代替临床试验，还是需要大规模临床试验结果。
百家争鸣之心血管
目前大部分ACS患者会接受阿司匹林联合氯吡格雷抗血小板治疗； 德里（Derry）等的研究表明，长期使用阿司匹林致消化道出血的发生
研究表明，ACS患者合并严重胃肠道出血的发生率为3%。
消化道出血死亡率高
ACS合并胃肠道出血的患者预后差，死亡率高达36.3%，与未合并胃肠道出血
的ACS患者相比具有显著差异。
出血的高危因素
既往有上消化道出血病史、活动性消化性溃疡、既往有消化性溃疡史（特别是具
有溃疡并发症者）、已知的胃息肉和恶性肿瘤等。
氧化水解形成具有药理活性的硫醇衍生物，该活性代谢产物不可逆地 与血小板二磷酸腺苷受体P2Y12结合，最终抑制纤维蛋白原受体
GPⅡb/Ⅲa活化，从而抑制血小板聚集。
PPI也主要通过CYP2C19和CYP3A4同工酶在肝脏代谢。 PPI与氯吡格雷合用时可能会因共同竞争CYP450同工酶的相同结合位点
而发生药物相互作用，其程度取决于与CYP450同工酶相对亲合力的大
小，高亲和力化合物将与酶结合并抑制低亲和力化合物的生物转化。
PPI与氯吡格雷的药代学影响
Ki值越小表示对该同工酶抑制效力越强
PPI与氯吡格雷的药代学影响
对CYP2C19的抑制强度：兰索拉唑>奥美拉唑>埃索美拉唑>泮托拉唑>雷贝拉唑
最新资料
最新资料

Thromb Haemost. 2009 Apr;101(4):714-9. Impact of proton pump inhibitors on the antiplatelet effects of clopidogrel. Patients receiving dual antiplatelet treatment with aspirin and clopidogrel are commonly treated with proton pump inhibitors (PPIs). Attenuating effects on platelet response to clopidogrel have been reported solely for the PPI omeprazole. PPIs differ in their metabolisation properties as well as their potential for drug-drug interactions. The aim of this study was to investigate the impact of different PPIs (pantoprazole, omeprazole, esomeprazole) on platelet response to clopidogrel in patients with previous coronary stent placement under chronic clopidogrel treatment. In a crosssectional observational study, consecutive patients under clopidogrel maintenance treatment (n = 1,000) scheduled for a control coronary angiography were enrolled. Adenosine diphosphate (ADP)induced platelet aggregation (in AU*min) was measured with multiple electrode platelet aggregometry (MEA). From the entire study population, 268 (26.8%) patients were under PPI treatment at the time point of platelet function testing (pantoprazole, n = 162; omeprazole, n = 64; esomeprazole, n = 42). Platelet aggregation (median [interquartile range]) was significantly higher in patients with omeprazole treatment (295.5 [193.5-571.2] AU*min) compared to patients without PPI treatment (220.0 [143.8-388.8] AU*min; p = 0.001). Platelet aggregation was similar in patients with pantoprazole (226.0 [150.0-401.5] AU*min) or esomeprazole (209.0 [134.8-384.8] AU*min) treatment compared to patients without PPI treatment (p = 0.69 and p = 0.88, respectively). Attenuating effects of concomitant PPI treatment on platelet response to clopidogrel were restricted to the use of omeprazole. No attenuating effects on platelet response to clopidogrel were observed for pantoprazole or esomeprazole. Specifically designed and randomized clinical studies are needed to define the impact of concomitant PPI treatment on adverse events after percutaneous coronary intervention.
J Med. 2005 Jan 20;352(3):238-44.
2008年美国心脏病学会基金会（ACCF）/美国胃肠病学会（ACG）/AHA联合公布
的专家共识对氯吡格雷替代阿司匹林提出质疑，建议有消化道溃疡复发风险者
采用阿司匹林联合PPI治疗，另外，急性心梗后服用阿司匹林的患者同时加用质
子泵抑制剂（PPI）。
PPI 相关指南与共识
2007年美国心脏病学会/美国心脏学会（ACC / AHA）发表指南指出，既往有消
化道出血病史者，在单独或联用阿司匹林和氯吡格雷时，可加用质子泵抑制剂 （PPI）以降低再出血风险；
Aspirin plus PPI safer than clopidogrel if there is history of GI bleeding. N Engl
冤家对头—东窗事发
为了降低抗血小板治疗患者的消化道出血风险，加用质子
泵抑制剂（PPI）似乎已成为临床常规，但今年初《加拿大 医学会杂志》[CMAJ 2009，180(7):713]和《美国医学会杂 志》[JAMA 2009，301(9):937]发表的两项大规模回顾性研 究对这一用法提出了质疑。两项研究均显示，氯吡格雷与 PPI联用增加心血管事件发生风险。此后美国FDA也发出警 告，提醒医生警惕以上两药联用的风险。
识；
权衡抗血小板治疗降低“心血管缺血风险”和 增加“消化道出血风险”
的利弊以及应用PPI有利止血和其减弱氯吡格雷作用之利弊应侧重考虑
心血管缺血风险；
PPI预防性用药需有针对性：消化性溃疡病史无出血但有幽门螺杆菌感
染；近年有消化道溃疡出血病史；需双重抗血小板制剂。超过下列一项 因素者：年龄≥60岁、应用皮质激素超过6日或更长时间、脓毒症患者， 也应考虑应用PPI。一般疗程不超过8周；

OBJECTIVE: To evaluate the interaction between clopidogrel and proton pump inhibitors (PPIs). DATA SOURCES: Literature retrieval was accessed through PubMed (1980- January 2009), abstracts from 2008 American Heart Association and 2009 Society of Cardiovascular Angiography and Interventions Scientific Sessions, and media press releases using the terms clopidogrel, proton pump inhibitors, cytochrome 2C19, genetic cytochrome P450 polymorphisms, and drug interaction. In addition, reference citations from publications identified in the search were reviewed. STUDY SELECTION AND DATA EXTRACTION: Relevant original research articles and review articles were evaluated. Articles were selected if they were published in English and focused on any of the key words or appeared to have substantial content addressing the drug interaction. DATA SYNTHESIS: Recent attention has been placed on a potential interaction observed between clopidogrel and the widely used PPIs. Preliminary evidence suggests that omeprazole interacts with clopidogrel, reducing clopidogrel's antiplatelet effects as measured by various laboratory tests. Most data indicate that the interaction involves the competitive inhibition of the CYP2C19 isoenzyme. The interaction appears to be clinically significant, as several retrospective analyses have shown an increase in adverse cardiovascular outcomes when PPIs and clopidogrel are used concomitantly. However, this may not be a class effect. CONCLUSIONS: Available data suggest that omeprazole is the PPI most likely to have a significant interaction with clopidogrel. Further studies are needed to determine that an interaction between the other PPIs and clopidogrel does not exist. In situations in which both clopidogrel and a PPI are indicated, pantoprazole should be used since it is the PPI least likely to interact with clopidogrel.