Koga Seiji, Ikeda Satoshi, Akashi Ryohei, Yonekura Tsuyoshi, Kawano Hiroaki, Maemura Koji
Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan.
Circ Rep. 2020 Dec 18;3(1):26-33. doi: 10.1253/circrep.CR-20-0124.
Vonoprazan is a potassium-competitive acid blocker increasingly used in Japan to prevent upper gastrointestinal bleeding in patients undergoing dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). Cytochrome P450 (CYP) 3A4 is involved in the primary metabolism of both vonoprazan and prasugrel. This raises concern about the possibility of a CYP3A4-mediated drug-drug interaction between vonoprazan and prasugrel that may lead to attenuation of prasugrel's antiplatelet effect. We evaluated 88 PCI patients who were taking either vonoprazan (n=45) or proton pump inhibitors (PPIs; n=43) in combination with DAPT (aspirin and prasugrel). Platelet reactivity on prasugrel was assessed using the VerifyNow P2Y assay. The primary endpoint was comparison of P2Y reaction units (PRU) between patients on vonoprazan and PPIs. PRU >208 and <85 were defined as high (HPR) and low (LPR) on-treatment platelet reactivity for prasugrel. PRU was comparable between patients receiving vonoprazan and PPIs (169±52 vs. 179±61, respectively; P=0.75). There were no significant differences between the vonoprazan and PPI groups in the prevalence of HPR (22% vs. 37%, respectively; P=0.16) and LPR (4 vs. 7%, respectively; P=0.48). The results were consistent regardless of the type of clinical presentation and DAPT duration. PRU under DAPT with aspirin plus prasugrel in patients receiving vonoprazan was not significantly different from that in patients receiving PPIs after PCI in routine clinical practice.
沃克帕唑是一种钾竞争性酸阻滞剂，在日本越来越多地用于预防经皮冠状动脉介入治疗（PCI）后接受双联抗血小板治疗（DAPT）的患者发生上消化道出血。细胞色素P450（CYP）3A4参与沃克帕唑和普拉格雷的主要代谢。这引发了人们对沃克帕唑和普拉格雷之间可能存在CYP3A4介导的药物相互作用的担忧，这种相互作用可能导致普拉格雷的抗血小板作用减弱。我们评估了88例接受DAPT（阿司匹林和普拉格雷）联合沃克帕唑（n = 45）或质子泵抑制剂（PPI；n = 43）治疗的PCI患者。使用VerifyNow P2Y检测评估普拉格雷的血小板反应性。主要终点是比较服用沃克帕唑和PPI的患者之间的P2Y反应单位（PRU）。PRU>208和<85分别被定义为普拉格雷治疗期间的高（HPR）和低（LPR）血小板反应性。接受沃克帕唑和PPI的患者之间的PRU相当（分别为169±52和179±61；P = 0.75）。沃克帕唑组和PPI组在HPR患病率（分别为22%和37%；P = 0.16）和LPR患病率（分别为4%和7%；P = 0.48）方面无显著差异。无论临床表现类型和DAPT持续时间如何，结果都是一致的。在常规临床实践中，接受沃克帕唑治疗的患者在阿司匹林加普拉格雷的DAPT下的PRU与PCI后接受PPI治疗的患者的PRU无显著差异。
