Abstract：
BACKGROUND: Among patients treated with a novel oral anticoagulant (NOAC) undergoing percutaneous coronary intervention (PCI), combination therapy with clopidogrel (ie, known as dual antithrombotic therapy [DAT]) is the treatment of choice. However, there are concerns for individuals with impaired response to clopidogrel.
OBJECTIVE: The authors sought to assess the pharmacodynamic (PD) effects of clopidogrel vs low-dose ticagrelor in patients with impaired clopidogrel response assessed by the ABCD-GENE score.
METHODS: This was a prospective, randomized PD study of NOAC-treated patients undergoing PCI. Patients with an ABCD-GENE score ≥10 (n = 39), defined as having impaired clopidogrel response, were randomized to low-dose ticagrelor (n = 20; 60 mg twice a day) or clopidogrel (n = 19; 75 mg once a day). Patients with an ABCD-GENE score <10 (n = 42) were treated with clopidogrel (75 mg once a day; control cohort). PD assessments at baseline and 30 days post-randomization (trough and peak) were performed to assess P2Y12 signaling (VerifyNow P2Y12 reaction units [PRU], light transmittance aggregometry, and vasodilator-stimulated phosphoprotein); makers of thrombosis not specific to P2Y12 signaling were also assessed. The primary endpoint was PRU (trough levels) at 30 days.
RESULTS: At 30 days, PRU levels were reduced with ticagrelor-based DAT compared with clopidogrel-based DAT at trough (23.0 [Q1-Q3: 3.0-46.0] vs 154.5 [Q1-Q3: 77.5-183.0]; P < 0.001) and peak (6.0 [Q1-Q3: 4.0-14.0] vs 129.0 [Q1-Q3: 66.0-171.0]; P < 0.001). Trough PRU levels in the control arm (104.0 [Q1-Q3: 35.0-167.0]) were higher than ticagrelor-based DAT (P = 0.005) and numerically lower than clopidogrel-based DAT (P = 0.234). Results were consistent by light transmittance aggregometry and vasodilator-stimulated phosphoprotein. Markers measuring other pathways leading to thrombus formation were largely unaffected.
CONCLUSIONS: In NOAC-treated patients undergoing PCI with an ABCD-GENE score ≥10, ticagrelor-based DAT using a 60-mg, twice-a-day regimen reduced platelet P2Y12 reactivity compared with clopidogrel-based DAT. (Tailoring P2Y12 Inhibiting Therapy in Patients Requiring Oral Anticoagulation After PCI [SWAP-AC-2]; NCT04483583).
OBJECTIVE: The authors sought to assess the pharmacodynamic (PD) effects of clopidogrel vs low-dose ticagrelor in patients with impaired clopidogrel response assessed by the ABCD-GENE score.
METHODS: This was a prospective, randomized PD study of NOAC-treated patients undergoing PCI. Patients with an ABCD-GENE score ≥10 (n = 39), defined as having impaired clopidogrel response, were randomized to low-dose ticagrelor (n = 20; 60 mg twice a day) or clopidogrel (n = 19; 75 mg once a day). Patients with an ABCD-GENE score <10 (n = 42) were treated with clopidogrel (75 mg once a day; control cohort). PD assessments at baseline and 30 days post-randomization (trough and peak) were performed to assess P2Y12 signaling (VerifyNow P2Y12 reaction units [PRU], light transmittance aggregometry, and vasodilator-stimulated phosphoprotein); makers of thrombosis not specific to P2Y12 signaling were also assessed. The primary endpoint was PRU (trough levels) at 30 days.
RESULTS: At 30 days, PRU levels were reduced with ticagrelor-based DAT compared with clopidogrel-based DAT at trough (23.0 [Q1-Q3: 3.0-46.0] vs 154.5 [Q1-Q3: 77.5-183.0]; P < 0.001) and peak (6.0 [Q1-Q3: 4.0-14.0] vs 129.0 [Q1-Q3: 66.0-171.0]; P < 0.001). Trough PRU levels in the control arm (104.0 [Q1-Q3: 35.0-167.0]) were higher than ticagrelor-based DAT (P = 0.005) and numerically lower than clopidogrel-based DAT (P = 0.234). Results were consistent by light transmittance aggregometry and vasodilator-stimulated phosphoprotein. Markers measuring other pathways leading to thrombus formation were largely unaffected.
CONCLUSIONS: In NOAC-treated patients undergoing PCI with an ABCD-GENE score ≥10, ticagrelor-based DAT using a 60-mg, twice-a-day regimen reduced platelet P2Y12 reactivity compared with clopidogrel-based DAT. (Tailoring P2Y12 Inhibiting Therapy in Patients Requiring Oral Anticoagulation After PCI [SWAP-AC-2]; NCT04483583).
摘要：
背景：在接受经皮冠状动脉介入治疗（PCI）的新型口服抗凝剂（NOAC）治疗的患者中，与氯吡格雷联合治疗(即，被称为双重抗血栓治疗[DAT]）是首选治疗方法。然而,对氯吡格雷反应受损的个体存在担忧.
目的：评估氯吡格雷与氯吡格雷的药效学（PD）效应低剂量替格瑞洛治疗氯吡格雷反应受损的患者的影响，通过ABCD-基因评分评估。
方法：这是一个前瞻性的，接受PCI的NOAC治疗患者的随机PD研究。ABCD-GENE评分≥10的患者（n=39），定义为氯吡格雷反应受损，患者随机接受低剂量替格瑞洛（n=20；60mg/bid）或氯吡格雷（n=19；75mg/qd）。使用氯吡格雷(75mg/qd;对照队列)治疗的患者为ABCD-GENE<10(n=42)。在基线和随机化后30天（波谷和峰值）进行PD评估以评估P2Y12信号传导[VerifyNowP2Y12反应单位（PRU），透光率聚集测定法(LTA)，和血管扩张剂刺激的磷蛋白（VASP）]；还评估了非P2Y12信号特异性血栓形成的标志物。主要终点是30天的PRU（波谷水平）。
结果：在30天，与基于氯吡格雷的DAT相比，基于替格瑞洛的DAT降低了PRU水平（23.0[3.0-46.0]vs.154.5[77.5-183.0]；p<0.001）和峰值（6.0[4.0-14.0]vs.129.0[66.0-171.0]；p<0.001）。对照组中的低PRU水平（104.0[35.0-167.0]）高于基于替格瑞洛的DAT（p=0.005），数值上低于基于氯吡格雷的DAT（p=0.234）。LTA和VASP结果一致。测量导致血栓形成的其他途径的标记在很大程度上不受影响。
结论：在NOAC治疗的PCI患者中，与基于氯吡格雷的DAT相比，使用60mgbid方案的基于替格瑞洛的DAT降低了血小板P2Y12反应性。
目的：评估氯吡格雷与氯吡格雷的药效学（PD）效应低剂量替格瑞洛治疗氯吡格雷反应受损的患者的影响，通过ABCD-基因评分评估。
方法：这是一个前瞻性的，接受PCI的NOAC治疗患者的随机PD研究。ABCD-GENE评分≥10的患者（n=39），定义为氯吡格雷反应受损，患者随机接受低剂量替格瑞洛（n=20；60mg/bid）或氯吡格雷（n=19；75mg/qd）。使用氯吡格雷(75mg/qd;对照队列)治疗的患者为ABCD-GENE<10(n=42)。在基线和随机化后30天（波谷和峰值）进行PD评估以评估P2Y12信号传导[VerifyNowP2Y12反应单位（PRU），透光率聚集测定法(LTA)，和血管扩张剂刺激的磷蛋白（VASP）]；还评估了非P2Y12信号特异性血栓形成的标志物。主要终点是30天的PRU（波谷水平）。
结果：在30天，与基于氯吡格雷的DAT相比，基于替格瑞洛的DAT降低了PRU水平（23.0[3.0-46.0]vs.154.5[77.5-183.0]；p<0.001）和峰值（6.0[4.0-14.0]vs.129.0[66.0-171.0]；p<0.001）。对照组中的低PRU水平（104.0[35.0-167.0]）高于基于替格瑞洛的DAT（p=0.005），数值上低于基于氯吡格雷的DAT（p=0.234）。LTA和VASP结果一致。测量导致血栓形成的其他途径的标记在很大程度上不受影响。
结论：在NOAC治疗的PCI患者中，与基于氯吡格雷的DAT相比，使用60mgbid方案的基于替格瑞洛的DAT降低了血小板P2Y12反应性。
