Wessex Cardiothoracic Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Faculty of Medicine, University of Southampton, Southampton, UK.
J Thromb Haemost. 2015 Jun;13(6):920-30. doi: 10.1111/jth.12909. Epub 2015 Apr 23.
Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor, mostly clopidogrel, is the default therapy in both acute coronary syndrome (ACS) and after intracoronary stents. It is well established that responses to antiplatelet therapy (APT), particularly clopidogrel, are subject to considerable interindividual variability.
We investigated whether responses to APT in individuals vary significantly over time.
Simultaneous assay with VerifyNow(™) and short thrombelastography (s-TEG) was performed before and at four time points over 6 months after hospital discharge in 40 patients receiving DAPT. Serum thromboxane B2 levels were also measured.
While aspirin response units (ARU) by VerifyNow(™) and serum thromboxane B2 levels remained stable over time, arachidonic acid (AA)-mediated platelet aggregation with s-TEG (i.e. area under the curve at 15 min in AA channel, AUC15AA ) increased at 1 week compared with predischarge (P < 0.008). In addition, platelet reactivity units (PRU) by VerifyNow(™) (P = 0.046) and adenosine diphosphate (ADP)-mediated platelet aggregation with s-TEG (i.e. AUC15ADP ) also increased at 1 week compared with predischarge (P = 0.026). There were no significant changes in either platelet reactivity or rates of high on-treatment platelet reactivity while receiving clopidogrel beyond 1 week.
This study demonstrates important variability in responses to APT within individuals between predischarge and 1 week but not thereafter. The use of a single early (predischarge) platelet function assay as an indicator of future response may therefore be flawed. The design of future strategies to assess individual responses for tailored therapy needs to take this into account.
在急性冠脉综合征（ACS）和冠状动脉内支架置入后，双重抗血小板治疗（DAPT）采用阿司匹林和 P2Y12 抑制剂（主要是氯吡格雷）。众所周知，抗血小板治疗（APT），尤其是氯吡格雷的反应存在相当大的个体间差异。
我们研究个体对 APT 的反应是否随时间有显著变化。
40 例接受 DAPT 的患者在出院后 6 个月内的 4 个时间点进行了VerifyNow（™）和短血栓弹力图（s-TEG）的同步检测，并在出院前和出院后进行了检测。还测量了血清血栓素 B2 水平。
尽管VerifyNow（™）的阿司匹林反应单位（ARU）和血清血栓素 B2 水平随时间保持稳定，但 s-TEG 中花生四烯酸（AA）介导的血小板聚集（即 AA 通道 15 分钟时的曲线下面积，AUC15AA）在 1 周时与出院前相比增加（P < 0.008）。此外，VerifyNow（™）的血小板反应单位（PRU）（P = 0.046）和 s-TEG 中二磷酸腺苷（ADP）介导的血小板聚集（即 AUC15ADP）也在 1 周时与出院前相比增加（P = 0.026）。在接受氯吡格雷治疗超过 1 周后，血小板反应或高治疗反应血小板的发生率均无显著变化。
本研究表明，个体在出院前和 1 周之间对 APT 的反应存在重要的个体内变异性，但此后则没有。因此，使用单一的早期（出院前）血小板功能检测作为未来反应的指标可能存在缺陷。未来评估个体化反应以制定个体化治疗策略的设计需要考虑到这一点。
