Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenhe District, Shenyang 110016, Liaoning, China.
Department of Cardiology, the Second Hospital of Jilin University, Changchun, Jilin, China.
Eur Heart J Cardiovasc Pharmacother. 2022 Dec 2;8(8):806-814. doi: 10.1093/ehjcvp/pvac026.
Vicagrel, a novel antiplatelet prodrug to overcome the residual high platelet reactivity of clopidogrel induced by inactive metabolism and cytochrome P450 (CYP) 2C19 polymorphisms, provides favourable antiplatelet inhibition in healthy volunteers. However, its antiplatelet effect and safety in patients with coronary artery disease (CAD) are unclear.
This was a multicentre, randomized, double-blind, triple-dummy, dose-exploring phase II trial comparing the antiplatelet activity and safety of vicagrel at different doses vs. those of clopidogrel in patients with CAD undergoing percutaneous coronary intervention (PCI). The primary endpoint was inhibition of adenosine diphosphate (ADP)-induced platelet aggregation (%IPA) after loading and maintenance doses (LD/MD) at 28 days. Safety endpoints included adverse events (AEs) and Bleeding Academic Research Consortium-defined any bleeding. Pharmacokinetic (PK) profiles and the influence of CYP2C19 polymorphisms were explored in subgroup analysis. Two hundred and seventy-nine patients diagnosed with stable CAD (51.97%), unstable angina (40.86%), and myocardial infarction (7.17%) were randomized to receive vicagrel 20/5 mg (LD/MD), 24/6 mg, or 30/7.5 mg or clopidogrel 300/75 mg in combination with aspirin. %IPAs on Day 28 were 30.19%, 35.02%, 45.61%, and 32.55% for vicagrel 20/5, 24/6, and 30/7.5 mg and clopidogrel, respectively, and were comparable across all groups (P = 0.0694). The plasma concentration of the vicagrel active metabolite M15-2 had a similar area under curve and Tmax to those of clopidogrel. There were no significant differences in AEs (4.35%, 0%, 1.45%, and 5.56% for vicagrel 20/5, 24/6, and 30/7.5 mg and clopidogrel, P = 0.6667) or any bleeding (13.04%, 14.06%, 11.59%, and 11.11% for vicagrel 20/5, 24/6, and 30/7.5 mg and clopidogrel, respectively, P = 0.95) across four groups. %IPAs and PK profiles of vicagrel did not vary significantly among different CYP2C19 metabolizers.
Vicagrel had comparable antiplatelet effect and safety to clopidogrel in patients with CAD undergoing PCI.
维卡格雷是一种新型抗血小板前药，可克服氯吡格雷因无活性代谢和细胞色素 P450（CYP）2C19 多态性引起的血小板反应性残留升高，可在健康志愿者中提供良好的抗血小板抑制作用。然而，其在冠心病（CAD）患者中的抗血小板作用和安全性尚不清楚。
这是一项多中心、随机、双盲、三盲、剂量探索性 II 期试验，比较了不同剂量维卡格雷与 CAD 经皮冠状动脉介入治疗（PCI）患者氯吡格雷的抗血小板活性和安全性。主要终点是 28 天时负荷和维持剂量（LD/MD）后腺苷二磷酸（ADP）诱导的血小板聚集抑制率（%IPA）。安全性终点包括不良事件（AE）和 Bleeding Academic Research Consortium 定义的任何出血。亚组分析中探讨了药代动力学（PK）特征和 CYP2C19 多态性的影响。279 例稳定型 CAD（51.97%）、不稳定型心绞痛（40.86%）和心肌梗死（7.17%）患者被随机分配接受维卡格雷 20/5mg（LD/MD）、24/6mg 或 30/7.5mg 或氯吡格雷 300/75mg 联合阿司匹林治疗。第 28 天的%IPA 分别为维卡格雷 20/5、24/6 和 30/7.5mg 组为 30.19%、35.02%、45.61%和氯吡格雷组为 32.55%，各组间无显著差异（P=0.0694）。维卡格雷活性代谢物 M15-2 的血浆浓度与氯吡格雷相似，具有相似的曲线下面积和 Tmax。维卡格雷 20/5、24/6 和 30/7.5mg 组与氯吡格雷组的 AE（4.35%、0%、1.45%和 5.56%，P=0.6667）或任何出血（13.04%、14.06%、11.59%和 11.11%，P=0.95）发生率无显著差异。不同 CYP2C19 代谢者的维卡格雷的%IPA 和 PK 特征无显著差异。
维卡格雷在 CAD 接受 PCI 治疗的患者中与氯吡格雷具有相当的抗血小板作用和安全性。
