Department of Cardiovascular Medicine, School of Medicine, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, Japan.
Heart Vessels. 2021 Apr;36(4):442-451. doi: 10.1007/s00380-020-01714-w. Epub 2020 Oct 28.
Compared to clopidogrel, prasugrel has a lower incidence of ischemic events following percutaneous coronary intervention (PCI) because of an early reduction during the acute phase in P2Y12 reaction units (PRU). The objective of this study was to compare the antiplatelet effect and vascular endothelial function of both drugs during the chronic phase after PCI. Patients who had undergone PCI and were confirmed to have no restenosis by follow-up coronary angiography under dual anti-platelet therapy with clopidogrel (75 mg/day) and aspirin (100 mg/day) were randomized to either continue clopidogrel or switch to prasugrel (3.75 mg/day). At baseline, prior to randomization we determined the CYP2C19 genotype. At the baseline and 24 weeks after randomization, the P2Y12 reactivity unit (PRU) was measured using the VerifyNow™ P2Y12 assay. Endothelial function was evaluated by flow-mediated vasodilation (FMD) and reactive hyperemia peripheral arterial tonometry (RH-PAT), while and circulating CD34+/CD133+/CD45 progenitor cells were measured by flow cytometric analysis. Serum high-sensitivity C-reactive protein (hsCRP) level was also measured. The PRU was reduced significantly in the prasugrel group (P = 0.0008), especially in patients who were intermediate or poor metabolizers based on the CYP2C19 genotype (P < 0.0001). This reduction was not observed in the clopidogrel group. The number of CD34+/CD133+/CD45 cells increased in the clopidogrel group (P = 0.008), but not in the prasugrel group. The hsCRP, FMD and reactive hyperemia index measured by RH-PAT did not change in either group. Prasugrel is potentially better than clopidogrel for preventing thrombotic events, although clopidogrel may have an advantage over prasugrel in terms of preventing atherosclerotic events. Proper use of thienopyridine drugs based on the CYP2C19 genotype has promising clinical potential.
与氯吡格雷相比，普拉格雷在经皮冠状动脉介入治疗（PCI）后发生缺血事件的发生率较低，这是由于在急性期 P2Y12 反应单位（PRU）早期减少。本研究的目的是比较两种药物在 PCI 后慢性期的抗血小板作用和血管内皮功能。在接受 PCI 并在氯吡格雷（75mg/天）和阿司匹林（100mg/天）双联抗血小板治疗下通过随访冠状动脉造影确认无再狭窄的患者中，随机继续使用氯吡格雷或换用普拉格雷（3.75mg/天）。在基线时，在随机分组之前，我们确定了 CYP2C19 基因型。在基线和随机分组后 24 周，使用 VerifyNow™ P2Y12 测定法测定 P2Y12 反应单位（PRU）。通过血流介导的血管扩张（FMD）和反应性充血外周动脉张力计（RH-PAT）评估内皮功能，同时通过流式细胞术分析测量循环 CD34+/CD133+/CD45 祖细胞。还测量了血清高敏 C 反应蛋白（hsCRP）水平。普拉格雷组的 PRU 显著降低（P=0.0008），特别是根据 CYP2C19 基因型为中或差代谢者（P<0.0001）。氯吡格雷组未观察到这种降低。氯吡格雷组的 CD34+/CD133+/CD45 细胞数量增加（P=0.008），但普拉格雷组没有。两组的 hsCRP、FMD 和通过 RH-PAT 测量的反应性充血指数均未发生变化。普拉格雷在预防血栓事件方面可能优于氯吡格雷，尽管氯吡格雷在预防动脉粥样硬化事件方面可能优于普拉格雷。基于 CYP2C19 基因型正确使用噻吩吡啶类药物具有广阔的临床应用前景。
