Department of Cardiology, Patras University Hospital, Patras, Greece.
J Thromb Haemost. 2011 Dec;9(12):2379-85. doi: 10.1111/j.1538-7836.2011.04531.x.
High on-treatment platelet reactivity (HTPR) is frequent in patients on hemodialysis (HD) receiving clopidrogel.
The primary aim of this study was to determine the antiplatelet effects of prasugrel vs. high-dose clopidogrel in patients on HD with HTPR.
PATIENTS/METHODS: We performed a prospective, single-center, single-blind, investigator-initiated, randomized, crossover study to compare platelet inhibition by prasugrel 10 mg day(-1) with that by high-dose 150 mg day(-1) clopidogrel in 21 patients on chronic HD with HTPR. Platelet function was assessed with the VerifyNow assay, and genotyping was performed for CYP2C19*2 carriage.
The primary endpoint of platelet reactivity (PR, measured in P2Y12 reaction units [PRU]) was lower in patients receiving prasugrel (least squares [LS] estimate 156.6, 95% confidence interval [CI] 132.2-181.1) than in those receiving high-dose clopidogrel (LS 279.9, 95% CI 255.4-304.3), P < 0.001). The LS mean differences between the two treatments were - 113.4 PRU (95% CI - 152.9 to - 73.8, P < 0.001) and - 163.8 PRU (95% CI - 218.1 to - 109.2, P < 0.001) in non-carriers and carriers of at least one CYP2C19*2 allele, respectively. HTPR rates were lower for prasugrel than clopidogrel, in all patients (19% vs. 85.7%, P < 0.001) and in non-carriers (25.7% vs. 80%, P = 0.003). All carriers continued to show HTPR while receiving high-dose clopidogrel, but none showed it while receiving prasugrel.
In HD patients exhibiting HTPR following standard clopidogrel treatment, prasugrel 10 mg day(-1) is significantly more efficient than doubling the clopidogrel dosage in achieving adequate platelet inhibition. Neither effect seems to be influenced by carriage of the loss-of-function CYP2C19*2 allele.
接受氯吡格雷治疗的血液透析（HD）患者常出现高反应性血小板（HTPR）。
本研究的主要目的是确定普拉格雷与高剂量氯吡格雷在 HTPR 血液透析患者中的抗血小板作用。
患者/方法：我们进行了一项前瞻性、单中心、单盲、研究者发起的、随机、交叉研究，以比较 21 例 HTPR 慢性 HD 患者接受普拉格雷 10 mg/天与高剂量氯吡格雷 150 mg/天的血小板抑制作用。通过 VerifyNow 测定血小板功能，并进行 CYP2C19*2 携带的基因分型。
接受普拉格雷治疗的患者血小板反应性（PR，以 P2Y12 反应单位[PRU]测量）的主要终点较低（最小二乘[LS]估计值为 156.6，95%置信区间[CI]为 132.2-181.1）比接受高剂量氯吡格雷的患者（LS 279.9，95%CI 为 255.4-304.3），P<0.001）。两种治疗方法之间的 LS 平均差异分别为-113.4 PRU（95%CI -152.9 至-73.8，P<0.001）和-163.8 PRU（95%CI -218.1 至-109.2，P<0.001）在非携带者和至少携带一个 CYP2C19*2 等位基因的携带者中，分别为。普拉格雷治疗的 HTPR 发生率低于氯吡格雷，在所有患者中（19% vs. 85.7%，P<0.001）和非携带者中（25.7% vs. 80%，P=0.003）。所有携带者在接受高剂量氯吡格雷治疗时仍表现出 HTPR，但在接受普拉格雷治疗时均未出现。
在接受标准氯吡格雷治疗后出现 HTPR 的血液透析患者中，普拉格雷 10 mg/天的剂量明显比增加氯吡格雷剂量更有效，以达到充分的血小板抑制作用。这两种作用似乎都不受失活 CYP2C19*2 等位基因的影响。
