Guo Long Zhe, Kim Moo Hyun, Kim Tae Hyung, Park Jong Seong, Jin Enze, Shim Chang Heon, Choi Sun Young, Serebruany Victor L
Department of Cardiology, Dong-A University Hospital, Busan, South Korea.
Nephron. 2016;132(3):191-7. doi: 10.1159/000444027. Epub 2016 Feb 26.
Clopidogrel and aspirin combination remains a cornerstone for modern dual antiplatelet therapy (DAPT) following coronary stenting. Although monitoring is not currently recommended, certain high-risk cohorts may benefit from tailoring antiplatelet options to reduce thrombotic or/and hemorrhagic risks. Patients with diminished estimated glomerular filtration rate (eGFR) are prone to both vascular occlusions and bleeding events in whom monitoring may be especially advantageous. We compared the residual platelet reactivity assessed by 3 conventional tests during the maintenance antiplatelet therapy dependent on eGFR.
Post-stenting patients (n = 701) receiving aspirin 100 mg/daily and clopidogrel 75 mg/daily were prospectively enrolled in the cross-sectional single-center study. Patients were dichotomized into 5 groups: eGFR >90, 60-89, 30-59, <30 ml/min/1.73 m2, and dialysis. Platelet reactivity by VerifyNow™, light transmittance aggregometry (LTA), and Multiplate analyzer by multiple electrode platelet aggregometry (MEA) assays together with eGFR calculations were done simultaneously at 1 month after coronary stenting.
VerifyNow assay distinguished residual platelet reactivity dependent on eGFR deterioration (191 ± 72 vs. 216 ± 78 vs. 248 ± 80 vs. 264 ± 70 vs. 317 ± 96 PRU; p < 0.001). In contrast, LTA (34.3 ± 18.1 vs. 34.7 ± 18.1 vs. 38.0 ± 16.6 vs. 33.0 ± 17.3 vs. 34.1 ± 29.3%; p = 0.242), or MEA (37.2 ± 19.6 vs. 33.8 ± 18.4 vs. 38.6 ± 21.4 vs. 36.5 ± 20.5 vs. 38.3 ± 28.3 AU/min; p = 0.086) failed to triage platelet reactivity in renal patients. Agreement among assays to identify patients with impaired platelet reactivity and eGFR during antiplatelet therapy was low. The multivariable regression analyses confirmed the VerifyNow advantage, since the differences in the platelet reactivity were highly significant for all renal impairment (RI) groups. In contrast, LTA did not distinguish RI patients, and for the MEA, only RI5 (dialysis) cohort exhibit borderline significant decline of residual platelet reactivity.
Among 3 assays, VerifyNow was capable to reliably triage residual platelet reactivity in post-stenting DAPT patients dependent on the gradual decline of eGFR during therapy with clopidogrel and aspirin. These data should be confirmed in a large validation longitudinal trial, and may justify future platelet activity monitoring for potential regimen/dose adjustment in high-risk patients. The clinical implications of these data are still unclear, but may give an indication as to whether or when DAPT dose adjustment will become a reality.
氯吡格雷与阿司匹林联合用药仍是现代冠状动脉支架置入术后双重抗血小板治疗（DAPT）的基石。尽管目前不建议进行监测，但某些高危人群可能会从调整抗血小板方案以降低血栓形成或/和出血风险中获益。估计肾小球滤过率（eGFR）降低的患者既容易发生血管闭塞，也容易发生出血事件，对这些患者进行监测可能特别有益。我们比较了在维持抗血小板治疗期间，根据eGFR通过3种传统检测方法评估的残余血小板反应性。
前瞻性纳入接受每日100 mg阿司匹林和75 mg氯吡格雷治疗的支架置入术后患者（n = 701），进行横断面单中心研究。患者被分为5组：eGFR>90、60 - 89、30 - 59、<30 ml/min/1.73 m²以及透析组。在冠状动脉支架置入术后1个月，同时进行VerifyNow™检测、光透射聚集法（LTA）检测以及多电极血小板聚集法（MEA）检测血小板反应性，并计算eGFR。
VerifyNow检测能够区分依赖于eGFR降低的残余血小板反应性（PRU分别为191±72、216±78、248±80、264±70、317±96；p<0.001）。相比之下，LTA检测（分别为34.3±18.1、34.7±18.1、38.0±16.6、33.0±17.3、34.1±29.3%；p = 0.242）或MEA检测（分别为37.2±19.6、33.8±18.4、38.6±21.4、36.5±20.5、38.3±28.3 AU/min；p = 0.086）未能对肾病患者的血小板反应性进行分层。在抗血小板治疗期间，各检测方法识别血小板反应性受损和eGFR受损患者的一致性较低。多变量回归分析证实了VerifyNow检测的优势，因为所有肾功能损害（RI）组的血小板反应性差异都非常显著。相比之下，LTA检测无法区分RI患者，对于MEA检测，只有RI5（透析）组的残余血小板反应性有临界显著下降。
在3种检测方法中，VerifyNow能够可靠地对支架置入术后DAPT患者在氯吡格雷和阿司匹林治疗期间依赖于eGFR逐渐下降的残余血小板反应性进行分层。这些数据应在大型验证性纵向试验中得到证实，并且可能为未来对高危患者进行血小板活性监测以进行潜在的治疗方案/剂量调整提供依据。这些数据的临床意义仍不明确，但可能提示DAPT剂量调整是否以及何时会成为现实。
