Koziński Marek, Obońska Karolina, Stankowska Katarzyna, Navarese Eliano Pio, Fabiszak Tomasz, Stolarek Wioleta, Kasprzak Michał, Siller-Matula Jolanta Maria, Rość Danuta, Kubica Jacek, De Servi Stefano
Department of Cardiology and Inter nal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
Cardiol J. 2014;21(5):547-56. doi: 10.5603/CJ.a2014.0026. Epub 2014 Mar 27.
The aim of this study was to assess antiplatelet effect of prasugrel in acute coronary syndrome (ACS) patients with high on-treatment platelet reactivity (HTPR) on clopidogrel, undergoing percutaneous coronary intervention (PCI).
A prospective, platelet reactivity-guided, parallel-group, open-label study including 71 patients pretreated with clopidogrel 600 mg and assigned either to prasugrel (30 mg loading dose, 10 mg maintenance dose; n = 46) or clopidogrel (150 mg maintenance dose for 6 days and thereafter 75 mg maintenance dose; n = 25) regimen, based on vasodilator-stimulated phosphoprotein (VASP)-assessed platelet reactivity index (PRI; > 50% vs. ≤ 50%) measured next morning post-PCI.
Median PRI value after switch to prasugrel sharply declined at 24 h (70.0 [61.3-75.6] vs. 11.9 [6.8-25.7]%; p < 0.000001) and slightly but significantly rose between 24 h and 30 days (27.9 [15.5-46.8]%; p < 0.0006). In contrast, median PRI values in the clopidogrel group were similar at baseline and at 24 h (25.1 [13.7-40.2] vs. 22.0 [18.4-36.8]%; p = NS) and then modestly rose at 30 days (30.3 [20.4-45.7]%; p < 0.03). The prevalence of HTPR decreased in the prasugrel group between baseline and 24 h measurements (100.0 vs. 4.3%; p < 0.0001). Rates of patients with HTPR at 24 h and 30 days were similar in both groups, so were the tendencies in patterns of platelet inhibition evaluated with multiple electrode aggregometry as compared with the VASP assay.
Our study indicates that prasugrel overcomes HTPR on clopidogrel in the acute phase of interventionally treated ACS and maintains its antiplatelet potency in 30-day follow-up. Potential clinical benefits of personalized antiplatelet prasugrel-based therapy warrant further investigation in clinical ACS trials.
本研究旨在评估普拉格雷对接受经皮冠状动脉介入治疗（PCI）的急性冠状动脉综合征（ACS）患者中氯吡格雷治疗时高治疗期血小板反应性（HTPR）的抗血小板作用。
一项前瞻性、血小板反应性引导、平行组、开放标签研究，纳入71例预先接受600mg氯吡格雷治疗的患者，根据PCI术后次日早晨通过血管扩张剂刺激磷蛋白（VASP）评估的血小板反应性指数（PRI；>50% 与≤50%），将患者分为普拉格雷组（负荷剂量30mg，维持剂量10mg；n = 46）或氯吡格雷组（维持剂量150mg，共6天，之后维持剂量75mg；n = 25）。
转换为普拉格雷后，PRI中位数在24小时时急剧下降（70.0[61.3 - 75.6]% 对11.9[6.8 - 25.7]%；p < 0.000001），并在24小时至30天之间略有但显著上升（27.9[15.5 - 46.8]%；p < 0.0006）。相比之下，氯吡格雷组PRI中位数在基线和24小时时相似（25.1[13.7 - 40.2]% 对22.0[18.4 - 36.8]%；p = 无显著差异），然后在30天时适度上升（30.3[20.4 - 45.7]%；p < 0.03）。普拉格雷组中HTPR的患病率在基线和24小时测量之间下降（100.0% 对4.3%；p < 0.0001）。两组在24小时和30天时HTPR患者的比例相似，与VASP检测相比，用多电极聚集法评估的血小板抑制模式趋势也相似。
我们的研究表明，普拉格雷在接受介入治疗的ACS急性期克服了氯吡格雷治疗时的HTPR，并在30天随访中维持其抗血小板效力。基于普拉格雷的个性化抗血小板治疗的潜在临床益处值得在临床ACS试验中进一步研究。
