BACKGROUND It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y12 inhibitors. METHODS We conducted a randomized, open-label, assessor-blinded trial in which patients undergoing primary PCI with stent implantation were assigned in a 1:1 ratio to receive either a P2Y12 inhibitor on the basis of early CYP2C19 genetic testing (genotype-guided group) or standard treatment with either ticagrelor or prasugrel (standard-treatment group) for 12 months. In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and noncarriers received clopidogrel. The two primary outcomes were net adverse clinical events - defined as death from any cause, myocardial infarction, definite stent thrombosis, stroke, or major bleeding defined according to Platelet Inhibition and Patient Outcomes (PLATO) criteria - at 12 months (primary combined outcome; tested for noninferiority, with a noninferiority margin of 2 percentage points for the absolute difference) and PLATO major or minor bleeding at 12 months (primary bleeding outcome). RESULTS For the primary analysis, 2488 patients were included: 1242 in the genotype-guided group and 1246 in the standard-treatment group. The primary combined outcome occurred in 63 patients (5.1%) in the genotype-guided group and in 73 patients (5.9%) in the standard-treatment group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.0 to 0.7; P<0.001 for noninferiority). The primary bleeding outcome occurred in 122 patients (9.8%) in the genotype-guided group and in 156 patients (12.5%) in the standard-treatment group (hazard ratio, 0.78; 95% CI, 0.61 to 0.98; P = 0.04). CONCLUSIONS In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy for selection of oral P2Y12 inhibitor therapy was noninferior to standard treatment with ticagrelor or prasugrel at 12 months with respect to thrombotic events and resulted in a lower incidence of bleeding. (Funded by the Netherlands Organization for Health Research and Development; POPular Genetics ClinicalTrials.gov number, NCT01761786; Netherlands Trial Register number, NL2872.).

中文翻译：

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原发性PCI中口服P2Y12抑制剂的基因型指导策略。

背景技术尚不清楚接受初级经皮冠状动脉介入治疗（PCI）的患者是否受益于基因型指导的口服P2Y12抑制剂的选择。方法我们进行了一项随机，开放标签，评估人盲目的试验，在该试验中，在早期CYP2C19基因测试的基础上，以1：1的比例分配接受PCI支架植入的患者接受P2Y12抑制剂（基因型指导组）。 ）或替卡格雷或普拉格雷（标准治疗组）进行12个月的标准治疗。在基因型指导的组中，CYP2C19 * 2或CYP2C19 * 3功能丧失的等位基因携带者接受替加格雷或普拉格雷，非携带者接受氯吡格雷。两项主要预后为净不良临床事件-定义为因任何原因死亡，心肌梗死，明确的支架血栓形成，中风，或根据血小板抑制和患者结局（PLATO）标准定义的严重出血-在12个月时（主要合并结局；经测试为非劣效性，绝对劣势的非劣效性差为2个百分点），在12个月时发生PLATO大出血或轻度出血（主要出血结果）。结果初步分析包括2488例患者：基因型指导组为1242例，标准治疗组为1246例。基因型指导组的初始合并结局发生在63例患者（5.1％），标准治疗组发生在73例患者（5.9％）（绝对差异为-0.7个百分点； 95％的置信区间[CI]，- 2.0至0.7；对于非自卑者，P <0.001）。基因型引导组的主要出血结果发生在122例患者（9.8％）和156例患者中（12。标准治疗组为5％）（危险比为0.78; 95％CI为0.61至0.98; P = 0.04）。结论在接受原发性PCI的患者中，以CYP2C19基因型指导的口服P2Y12抑制剂治疗选择策略在血栓事件方面在12个月时不劣于替格格雷或普拉格雷的标准治疗，并导致出血发生率较低。（由荷兰卫生研究与发展组织资助； POPular Genetics ClinicalTrials.gov号为NCT01761786；荷兰试验注册号为NL2872。）。CYP2C19基因型指导的口服P2Y12抑制剂治疗选择策略在血栓形成事件方面在12个月内不劣于替卡格雷或普拉格雷的标准治疗，并导致较低的出血发生率。（由荷兰卫生研究与发展组织资助； POPular Genetics ClinicalTrials.gov号为NCT01761786；荷兰试验注册号为NL2872。）。CYP2C19基因型指导的口服P2Y12抑制剂治疗选择策略在血栓形成事件方面在12个月内不劣于替卡格雷或普拉格雷的标准治疗，并导致较低的出血发生率。（由荷兰卫生研究与发展组织资助； POPular Genetics ClinicalTrials.gov号为NCT01761786；荷兰试验注册号为NL2872。）。