Sibbing Dirk, Morath Tanja, Stegherr Julia, Braun Siegmund, Vogt Wolfgang, Hadamitzky Martin, Schömig Albert, Kastrati Adnan, von Beckerath Nicolas
Deutsches Herzzentrum and 1. Medizinische Klinik rechts der Isar, Technische Universität München, Munich, Germany.
Thromb Haemost. 2009 Apr;101(4):714-9.
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 cross-sectional 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 AUmin) 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] AUmin) compared to patients without PPI treatment (220.0 [143.8-388.8] AUmin; p = 0.001). Platelet aggregation was similar in patients with pantoprazole (226.0 [150.0-401.5] AUmin) 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.
接受阿司匹林和氯吡格雷双重抗血小板治疗的患者通常会同时接受质子泵抑制剂(PPI)治疗。据报道,仅质子泵抑制剂奥美拉唑对血小板对氯吡格雷的反应有减弱作用。不同的质子泵抑制剂在代谢特性以及药物相互作用的可能性方面存在差异。本研究的目的是调查在慢性氯吡格雷治疗下,不同的质子泵抑制剂(泮托拉唑、奥美拉唑、埃索美拉唑)对既往有冠状动脉支架置入史患者血小板对氯吡格雷反应的影响。在一项横断面观察性研究中,纳入了连续接受氯吡格雷维持治疗(n = 1000)且计划进行冠状动脉造影检查的患者。使用多电极血小板聚集仪(MEA)测量二磷酸腺苷(ADP)诱导的血小板聚集(以AUmin为单位)。在血小板功能检测时间点,整个研究人群中有268例(26.8%)患者正在接受PPI治疗(泮托拉唑,n = 162;奥美拉唑,n = 64;埃索美拉唑,n = 42)。与未接受PPI治疗的患者(220.0 [143.8 - 388.8] AUmin;p = 0.001)相比,接受奥美拉唑治疗的患者血小板聚集(中位数[四分位间距])显著更高(295.5 [193.5 - 571.2] AUmin)。与未接受PPI治疗的患者相比,接受泮托拉唑(226.0 [150.0 - 401.5] AUmin)或埃索美拉唑(209.0 [134.8 - 384.8] AU*min)治疗的患者血小板聚集相似(p分别为0.69和0.88)。PPI联合治疗对血小板对氯吡格雷反应的减弱作用仅限于使用奥美拉唑。未观察到泮托拉唑或埃索美拉唑对血小板对氯吡格雷反应有减弱作用。需要进行专门设计的随机临床研究来确定PPI联合治疗对经皮冠状动脉介入治疗后不良事件的影响。