Zou Duowu, Goh Khean-Lee
Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Department of Gastroenterology and Hepatology, University of Malaya, Kuala Lumpur, Malaysia.
J Gastroenterol Hepatol. 2017 Jun;32(6):1152-1159. doi: 10.1111/jgh.13712.
Both proton pump inhibitors (PPIs) and clopidogrel are widely prescribed in the Asia-Pacific population. PPIs are the mainstay therapeutic agents for prophylaxis against aspirin gastropathy and for acid-related disorders including gastroesophageal reflux disease. They are also co-prescribed with oral anticoagulant agents and with dual-antiplatelet therapy for the treatment and prevention of gastrointestinal bleeding. Clopidogrel belongs to the drug class of thienopyridines and is currently the most widely prescribed oral anticoagulant agent either alone or in combination with aspirin. Platelet inhibition by clopidogrel is prone to significant inter-individual variability and is believed to be affected by several factors such as genetics and drug-drug interactions. Since it was first reported in 2009, the potential for drug-drug interactions between PPIs and clopidogrel has remained headline news, and its significance in clinical practice is the subject of an ongoing debate. For East Asian patients in particular, the clinical relevance of the interaction between PPIs and clopidogrel remains unclear because of conflicting data, as well as underrepresentation of East Asian subjects in landmark trials. Increased CYP2C19 genetic polymorphisms in individuals from Asia-Pacific countries only fuel the confusion. Recent studies in East Asian cohorts suggests that the potential of PPIs to attenuate the efficacy of clopidogrel could be minimized by the use of newer PPIs with weaker affinity for the CYP2C19 isoenzyme, namely, pantoprazole, dexlansoprazole, and rabeprazole. This review aims to help clinicians choose the most appropriate PPI for co-prescription with clopidogrel in patients from Asia-Pacific countries.
质子泵抑制剂（PPIs）和氯吡格雷在亚太人群中都被广泛应用。PPIs是预防阿司匹林性胃病以及治疗包括胃食管反流病在内的酸相关性疾病的主要治疗药物。它们还与口服抗凝剂以及双联抗血小板疗法联合使用，用于治疗和预防胃肠道出血。氯吡格雷属于噻吩并吡啶类药物，目前是单独或与阿司匹林联合使用时最广泛应用的口服抗凝剂。氯吡格雷对血小板的抑制作用存在显著的个体差异，并且被认为受多种因素影响，如遗传学和药物相互作用。自2009年首次报道以来，PPIs与氯吡格雷之间药物相互作用的可能性一直是头条新闻，其在临床实践中的重要性仍是一个持续争论的话题。特别是对于东亚患者，由于数据相互矛盾以及东亚受试者在具有里程碑意义的试验中代表性不足，PPIs与氯吡格雷之间相互作用的临床相关性仍不明确。亚太国家人群中CYP2C19基因多态性增加只会加剧这种混乱。最近对东亚队列的研究表明，通过使用对CYP2C19同工酶亲和力较弱的新型PPIs，即泮托拉唑、右兰索拉唑和雷贝拉唑，可以将PPIs减弱氯吡格雷疗效的可能性降至最低。本综述旨在帮助临床医生为亚太国家患者选择与氯吡格雷联合使用的最合适的PPIs。
