Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Department of Cardiology, King Fahd Armed Forces Hospital, Dhahran, Saudi Arabia.
BMC Cardiovasc Disord. 2020 Jun 3;20(1):268. doi: 10.1186/s12872-020-01558-2.
To mitigate the risk of stent thrombosis, patients treated by percutaneous coronary intervention (PCI) are administered dual anti-platelet therapy comprising aspirin and a platelet P2Y receptor inhibitor. Clopidogrel is a prodrug requiring activation by the cytochrome P450 enzyme, CYP2C19. In Saudi Arabia, it has been reported that approximately 26% of the population carries CYP2C19*2 and/or *3 loss-of-function polymorphisms in addition to a high prevalence of CVD.
This prospective (April 2013-December 2020) parallel assignment clinical trial focuses on ST-Elevation Myocardial Infarction (STEMI) patient outcomes. The clinical trial includes 1500 STEMI patients from two hospitals in the Eastern Province of Saudi Arabia. Patients are assigned to one of two groups; the control arm receives conventional therapy with clopidogrel, while in the active arm the Spartan RX CYP2C19 assay is used to determine the 2 genotype. Carriers of a CYP2C192 loss-of-function allele receive prasugrel or ticagrelor, while non-carriers are treated with clopidogrel. Follow-up is one year after primary PCI. The primary end point is the number of patients who develop an adverse major cardiovascular event, including recurrent MI, non-fatal stroke, cardiovascular death, or major bleeding one year after PCI.
The risk of stent thrombosis in PCI patients is usually reduced by dual anti-platelet therapy, comprising aspirin and a P2Y12 inhibitor, such as clopidogrel. However, clopidogrel requires activation by the cytochrome P450 enzyme, CYP2C19. Approximately 20% of the population are unable to activate clopidogrel as they possess the CYP2C19*2 loss-of function (LoF) allele. The primary goal of this trial is to study the benefits of treating only those patients that cannot activate clopidogrel with an alternative that has shown to be a more effective platelet inhibitor and does not require bioactivation by the cytochrome P450 enzyme. We expect an improvement in net clinical benefit outcome in the active arm patients, thus supporting pharmacogenetic testing in PCI patients post STEMI.
Trial registration name is "Bedside Testing of CYP2C19 Gene for Treatment of Patients with PCI with Antiplatelet Therapy" (number NCT01823185) retrospectively registered with clinicaltrials.gov on April 4, 2013. This trial is currently at the patient recruitment stage.
为了降低经皮冠状动脉介入治疗（PCI）患者的支架血栓形成风险，患者接受双联抗血小板治疗，包括阿司匹林和血小板 P2Y 受体抑制剂。氯吡格雷是一种前体药物，需要细胞色素 P450 酶 CYP2C19 激活。在沙特阿拉伯，据报道，大约 26%的人口携带 CYP2C192 和/或3 失活功能多态性，此外还有很高的心血管疾病患病率。
本前瞻性（2013 年 4 月至 2020 年 12 月）平行分配临床试验专注于 ST 段抬高型心肌梗死（STEMI）患者结局。该临床试验纳入了来自沙特阿拉伯东部两个医院的 1500 名 STEMI 患者。患者被分配到两组之一；对照组接受常规氯吡格雷治疗，而在活性组中，使用 Spartan RX CYP2C19 测定法确定2 基因型。携带 CYP2C192 失活等位基因的患者接受普拉格雷或替格瑞洛治疗，而非携带者接受氯吡格雷治疗。随访时间为 PCI 后 1 年。主要终点是 1 年后发生不良主要心血管事件（包括复发性 MI、非致命性中风、心血管死亡或大出血）的患者数量。
通过双重抗血小板治疗，包括阿司匹林和 P2Y12 抑制剂，如氯吡格雷，通常可以降低 PCI 患者的支架血栓形成风险。然而，氯吡格雷需要细胞色素 P450 酶 CYP2C19 激活。大约 20%的人群无法激活氯吡格雷，因为他们携带 CYP2C19*2 失活功能（LoF）等位基因。该试验的主要目标是研究仅治疗那些不能通过细胞色素 P450 酶激活氯吡格雷的患者的益处，用已被证明是更有效的血小板抑制剂的替代药物治疗，并且不需要细胞色素 P450 酶的生物激活。我们预计在活性臂患者中会改善净临床获益结局，从而支持 PCI 后 STEMI 患者的药物遗传学检测。
试验注册名称为“PCI 时用抗血小板治疗治疗患者的 CYP2C19 基因床边检测”（编号 NCT01823185），于 2013 年 4 月 4 日在 clinicaltrials.gov 上进行了回顾性注册。该试验目前处于患者招募阶段。
