Heart Diseases Institute, Hospital Universitario de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
Cardiovascular Institute, Hospital Clínico San Carlos, Madrid, Spain.
Thromb Res. 2019 Mar;175:95-101. doi: 10.1016/j.thromres.2019.01.021. Epub 2019 Jan 31.
There is compelling evidence supporting the association between high on-treatment platelet reactivity (HPR) and low on-treatment platelet reactivity (LPR) to clopidogrel with atherothrombotic and bleeding events, respectively. However, it is uncertain if current cutoff values should be used in prasugrel- or ticagrelor-treated subjects. The objective of this analysis was to evaluate the pharmacodynamic (PD) efficacy of P2Y antagonists in a contemporary real-world population.
This PD study included 988 patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) and receiving dual therapy with aspirin and a P2Y inhibitor (clopidogrel, prasugrel or ticagrelor). Platelet function was assessed at day 1 and day 30 post-PCI by VerifyNow P2Y12 assay, multiple electrode aggregometry and vasodilator-stimulated phosphoprotein (VASP) assay.
Clopidogrel-treated patients (n = 324) had greater platelet reactivity than those receiving ticagrelor (n = 469) or prasugrel (n = 195) at both time points (p < 0.001 for all comparisons). No difference between ticagrelor and prasugrel was observed at day 1 with the VerifyNow P2Y12 assay (51.5 ± 2.8 vs. 42.7 ± 3.5 PRUs; p = 0.298), whereas ticagrelor achieved greater platelet inhibition at day 30 (48.1 ± 2.5 vs. 89.2 ± 4.2 PRUs; p < 0.001). Similar results were obtained with the VASP assay. Both prasugrel and ticagrelor had markedly lower HPR rates than clopidogrel and very high rates of LPR at both time points.
Prasugrel and ticagrelor displayed more potent and consistent PD effects than clopidogrel in ACS patients undergoing PCI, with a trend towards greater platelet inhibition with ticagrelor during the maintenance phase of therapy compared to prasugrel.
有充分的证据表明,氯吡格雷治疗后血小板高反应性(HPR)和低反应性(LPR)分别与动脉血栓形成和出血事件相关。然而,目前的截断值是否适用于普拉格雷或替格瑞洛治疗的患者尚不确定。本分析的目的是评估在当代真实世界人群中,P2Y 拮抗剂的药效学(PD)疗效。
这项 PD 研究纳入了 988 例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,这些患者接受阿司匹林和 P2Y 抑制剂(氯吡格雷、普拉格雷或替格瑞洛)双联治疗。在 PCI 后第 1 天和第 30 天,通过 VerifyNow P2Y12 测定、多电极聚集测定和血管扩张刺激磷蛋白(VASP)测定评估血小板功能。
在两个时间点,氯吡格雷治疗的患者(n=324)的血小板反应性均高于接受替格瑞洛(n=469)或普拉格雷(n=195)治疗的患者(所有比较均 p<0.001)。在第 1 天,使用 VerifyNow P2Y12 测定,替格瑞洛和普拉格雷之间没有差异(51.5±2.8 与 42.7±3.5 PRU;p=0.298),而替格瑞洛在第 30 天达到更大的血小板抑制(48.1±2.5 与 89.2±4.2 PRU;p<0.001)。VASP 测定也得到了类似的结果。普拉格雷和替格瑞洛在两个时间点的 HPR 发生率均明显低于氯吡格雷,而 LPR 发生率非常高。
在接受 PCI 的 ACS 患者中,普拉格雷和替格瑞洛与氯吡格雷相比,PD 效果更强大且更一致,在维持治疗阶段,替格瑞洛的血小板抑制作用较普拉格雷有增加的趋势。