A genotype-guided strategy for oral P2Y12 inhibitors in primary PCI
Claassens, Daniel M.F.; Vos, Gerrit J.A.; Bergmeijer, Thomas O.; Hermanides, Renicus S.; Van’t Hof, Arnoud W.J.; Van Der Harst, Pim; Barbato, Emanuele; Morisco, Carmine; Tjon Joe Gin, Richard M.; Asselbergs, Folkert W.; Mosterd, Arend; Herrman, Jean Paul R.; Dewilde, Willem J.M.; Janssen, Paul W.A.; Kelder, Johannes C.; Postma, Maarten J.; De Boer, Anthonius; Boersma, Cornelis; Deneer, Vera H.M.; ten Berg, Jurriën M.
(2019) New England Journal of Medicine, volume 381, issue 17, pp. 1621 - 1631
(Article)
Abstract
BACKGROUND: It is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y 12 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 12
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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 P2Y 12 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.).
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Keywords: Administration, Oral, Aged, Clopidogrel/adverse effects, Coronary Thrombosis/prevention & control, Cytochrome P-450 CYP2C19/genetics, Female, Genotype, Hemorrhage/chemically induced, Humans, Intention to Treat Analysis, Male, Middle Aged, Percutaneous Coronary Intervention, Prasugrel Hydrochloride/adverse effects, Precision Medicine, Purinergic P2Y Receptor Antagonists/adverse effects, ST Elevation Myocardial Infarction/drug therapy, Single-Blind Method, Stents, Ticagrelor/adverse effects, General Medicine, Research Support, Non-U.S. Gov't, Randomized Controlled Trial, Multicenter Study, Journal Article
ISSN: 0028-4793
Publisher: Massachussetts Medical Society
Note: Funding Information: Supported by the Netherlands Organization for Health Research and Development, a Dutch government agency, as part of its efficiency research program (project 171102022). Spartan Bioscience provided the Spartan RX system and the reagents used free of charge. Dr. Asselbergs is supported by the University College London Hospitals National Institute for Health Research Biomedical Research Centre. Funding Information: The POPular Genetics trial was an investigator-initiated, randomized, open-label, assessor-blinded trial performed at 10 European sites (8 in the Netherlands, 1 in Belgium, and 1 in Italy). It was sponsored by the Netherlands Organization for Health Research and Development, and Spartan Bioscience provided the Spartan RX point-of-care system and the reagents for free. Neither entity had any role in the design or execution of the trial or in the analysis of the data. Details of the design have been published previously.13 Publisher Copyright: Copyright © 2019 Massachusetts Medical Society.
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