荷兰新维根市圣安东尼医院的Jurriën M. ten Berg与国际合作团队，分析了接受经皮冠状动脉介入治疗（PCI）的患者是否受益于基因型指导口服P2Y12抑制剂的选择。相关论文9月3日在线发表于《新英格兰医学杂志》。

研究组进行了一项随机、开放标签、评估者盲的试验，共招募了2488名患者，均初次接受支架植入PCI术，按1：1随机分组，其中1242例依据早期CYP2C19基因检测口服P2Y12抑制剂（基因型指导组），1246例接受替卡格雷或普拉格雷的标准治疗（标准治疗组），为期12个月。在基因型指导组中，携带CYP2C19*2或CYP2C19*3功能等位基因缺失的患者采用替卡格雷或普拉格雷治疗，而非携带者则采用氯吡格雷。

治疗12个月后，基因型指导组中有63例（5.1%）患者发生全因死亡、心肌梗死、明确的支架血栓形成、中风或大出血，标准治疗组中有73例（5.9%）。基因型指导组中有122例（9.8%）患者出现大出血或小出血，显著低于标准治疗组（156例，12.5%）。

综上，初次PCI的患者在CYP2C19基因型指导下选择性口服P2Y12抑制剂，其一年内的血栓性事件发生率并未显著高于替卡格雷或普拉格雷的标准治疗，且出血率明显降低。

附：英文原文

Title: A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI

Author: Daniel M.F. Claassens, M.D., Gerrit J.A. Vos, M.D., Thomas O. Bergmeijer, M.D., Renicus S. Hermanides, M.D., Ph.D., Arnoud W.J. van ’t Hof, M.D., Ph.D., Pim van der Harst, M.D., Ph.D., Emanuele Barbato, M.D., Ph.D., Carmine Morisco, M.D., Ph.D., Richard M. Tjon Joe Gin, M.D., Folkert W. Asselbergs, M.D., Ph.D., Arend Mosterd, M.D., Ph.D., Jean-Paul R. Herrman, M.D., Ph.D., Willem J.M. Dewilde, M.D., Ph.D., Paul W.A. Janssen, M.D., Ph.D., Johannes C. Kelder, M.D., Ph.D., Maarten J. Postma, Ph.D., Anthonius de Boer, M.D., Ph.D., Cornelis Boersma, Pharm.D., Ph.D., Vera H.M. Deneer, Pharm.D., Ph.D., and Jurriën M. ten Berg, M.D., Ph.D.

Issue&Volume: September 3, 2019

Abstract: 

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. opens in new tab; Netherlands Trial Register number, NL2872. opens in new tab.)