一种基于基因型的急性 ST 段抬高型心肌梗死直接经皮冠状动脉介入治疗中口服 P2Y12 抑制剂的策略。

A Genotype-Guided Strategy for Oral P2Y Inhibitors in Primary PCI.

机构信息

From the Department of Cardiology, St. Antonius Hospital, Nieuwegein (D.M.F.C., G.J.A.V., T.O.B., P.W.A.J., J.C.K., J.M.B.), the Department of Cardiology, Isala Hospital, Zwolle (R.S.H., A.W.J.H.), the Department of Cardiology, University Medical Center Maastricht, Maastricht (A.W.J.H.), the Department of Cardiology, Zuyderland Medical Center, Heerlen (A.W.J.H.), the Department of Cardiology, University Medical Center Groningen (P.H., J.M.B.), the Department of Pharmacy, University of Groningen (M.J.P.), and the Unit of Global Health, Department of Health Sciences, University of Groningen, University Medical Center Groningen (M.J.P., C.B.), Groningen, the Department of Cardiology, Rijnstate Hospital, Arnhem (R.M.T.J.G.), the Department of Cardiology, Division of Heart and Lungs (F.W.A.), and the Department of Clinical Pharmacy, Division of Laboratories, Pharmacy, and Biomedical Genetics (V.H.M.D.), University Medical Center Utrecht, and the Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (A.B.), Utrecht University, Utrecht, the Department of Cardiology, Meander Medical Center, Amersfoort (A.M.), the Department of Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam (J.-P.R.H.), and the Department of Cardiology, Amphia Hospital, Breda (W.J.M.D.) - all in the Netherlands; the Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy (E.B., C.M.); the Cardiovascular Research Center, Onze Lieve Vrouwe Hospital, Aalst (E.B.), and the Department of Cardiology, Imelda Hospital, Bonheiden (W.J.M.D.) - both in Belgium; and the Institute of Cardiovascular Science, Faculty of Population Health Sciences, and Health Data Research UK and Institute of Health Informatics, University College London, London (F.W.A.).

出版信息

N Engl J Med. 2019 Oct 24;381(17):1621-1631. doi: 10.1056/NEJMoa1907096. Epub 2019 Sep 3.

DOI:10.1056/NEJMoa1907096

PMID:31479209

Abstract

BACKGROUND

It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y 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 P2Y inhibitor on the basis of early 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 *2 or *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 genotype-guided strategy for selection of oral P2Y 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.).

摘要

背景

目前尚不清楚接受直接经皮冠状动脉介入治疗（PCI）的患者是否受益于基于基因型选择口服 P2Y 抑制剂。

方法

我们进行了一项随机、开放标签、评估者设盲试验，将接受支架植入的直接 PCI 患者以 1:1 的比例随机分为两组，一组基于早期基因检测（基因型指导组）接受 P2Y 抑制剂治疗，另一组接受替格瑞洛或普拉格雷标准治疗（标准治疗组），治疗时间为 12 个月。在基因型指导组中，携带2 或3 功能丧失等位基因的患者接受替格瑞洛或普拉格雷治疗，非携带者接受氯吡格雷治疗。主要复合终点为 12 个月时的净不良临床事件（任何原因导致的死亡、心肌梗死、明确的支架血栓形成、卒中和根据血小板抑制和患者结局（PLATO）标准定义的大出血）（主要终点，采用非劣效性检验，绝对差值的非劣效性边界为 2 个百分点）和 12 个月时 PLATO 大出血或小出血（主要出血终点）。

结果

对于主要分析，纳入了 2488 名患者：基因型指导组 1242 名，标准治疗组 1246 名。基因型指导组有 63 名（5.1%）患者发生主要复合终点事件，标准治疗组有 73 名（5.9%）患者发生主要复合终点事件（绝对差值，-0.7 个百分点；95%置信区间[CI]，-2.0 至 0.7；非劣效性检验 P<0.001）。基因型指导组有 122 名（9.8%）患者发生主要出血终点事件，标准治疗组有 156 名（12.5%）患者发生主要出血终点事件（风险比，0.78；95%CI，0.61 至 0.98；P=0.04）。

结论

在接受直接 PCI 的患者中，与接受替格瑞洛或普拉格雷标准治疗相比，口服 P2Y 抑制剂治疗的基因型指导策略在 12 个月时在血栓事件方面不劣效，且出血发生率更低。（由荷兰健康研究与发展组织资助；POPular Genetics 临床试验.gov 编号，NCT01761786；荷兰试验注册编号，NL2872.）