NIHR Cardiovascular Biomedical Research Unit and Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
J Thromb Haemost. 2011 Sep;9(9):1730-7. doi: 10.1111/j.1538-7836.2011.04419.x.
The rate of recovery of platelet function after discontinuation of P2Y(12) inhibitors depends on the reversibility of the antiplatelet effect and the extent of the on-treatment response. P2Y(12) inhibition increases the bleeding risk in patients requiring surgery.
To evaluate recovery of platelet function after discontinuation of ticagrelor vs. clopidogrel in stable coronary artery disease (CAD) patients with high levels of platelet inhibition (HPI) during the ONSET/OFFSET study.
Patients received aspirin 75-100 mg per day and either ticagrelor 90 mg twice-daily or clopidogrel 75 mg daily for 6 weeks. This subanalysis included patients with HPI after the last dose of maintenance therapy, defined as: inhibition of platelet aggregation (IPA) > 75% 4 h post-dose (ADP 20 μm, final extent); < 120 P2Y(12) reaction units 8 h post-dose (VerifyNow P2Y(12) assay); or platelet reactivity index < 50% 8 h post-dose (VASP-P assay).
IPA > 75% was observed in 39 out of 47 ticagrelor-treated and 17 out of 44 clopidogrel-treated patients. The rate of offset of IPA over 4-72 h was greater with ticagrelor (IPA %/hour slope: -1.11 vs. -0.67 for clopidogrel; P < 0.0001). Mean IPA was significantly lower with ticagrelor than clopidogrel between 48 and 168 h post-dose (P < 0.01). Similar findings were observed with the other assays. The average time for IPA to decline from 30% to 10% was 50.8 h with ticagrelor vs. 110.4 h with clopidogrel.
In patients with HPI, recovery of platelet function was more rapid after discontinuation of ticagrelor than clopidogrel leading to significantly greater platelet reactivity by 48 h after the last dose in the ticagrelor group.
血小板功能在停止使用 P2Y（12）抑制剂后恢复的速度取决于抗血小板作用的可逆性和治疗反应的程度。P2Y（12）抑制会增加需要手术的患者的出血风险。
在 ONSET/OFFSET 研究中，评估稳定型冠状动脉疾病（CAD）患者中高血小板抑制（HPI）患者停用替格瑞洛与氯吡格雷后血小板功能的恢复情况。
患者每日接受阿司匹林 75-100mg，同时接受替格瑞洛 90mg 每日两次或氯吡格雷 75mg 每日一次治疗 6 周。该亚组分析包括维持治疗最后一剂后 HPI 的患者，定义为：血小板聚集抑制（IPA）> 4 小时后> 75%（ADP 20μm，最终程度）；8 小时后< 120 P2Y（12）反应单位（VerifyNow P2Y（12）测定法）；或 8 小时后血小板反应指数< 50%（VASP-P 测定法）。
在 47 例接受替格瑞洛治疗的患者中有 39 例和 44 例接受氯吡格雷治疗的患者中有 17 例观察到 IPA > 75%。4-72 小时 IPA 消退率高于替格瑞洛（IPA%/小时斜率：替格瑞洛为-1.11，氯吡格雷为-0.67；P<0.0001）。与氯吡格雷相比，替格瑞洛在 48-168 小时后 IPA 明显更低（P<0.01）。其他检测方法也有类似的发现。IPA 从 30%降至 10%的平均时间为替格瑞洛 50.8 小时，氯吡格雷 110.4 小时。
在 HPI 患者中，停用替格瑞洛后血小板功能恢复较快，与氯吡格雷相比，在替格瑞洛组最后一剂后 48 小时时血小板反应性显著增加。
