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A Genotype-Guided Strategy for Oral P2Y(12) Inhibitors in Primary PCI

Claassens, D. M. F., Vos, G. J. A., Bergmeijer, T. O., Hermanides, R. S., van 't Hof, A. W. J., van der Harst, P., Barbato, E., Morisco, C., Gin, R. M. T. J., Asselbergs, F. W., Mosterd, A., Herrman, J-P. R., Dewilde, W. J. M., Janssen, P. W. A., Kelder, J. C., Postma, M. J., de Boer, A., Boersma, C., Deneer, V. H. M. & ten Berg, J. M., 24-Oct-2019, In : New England Journal of Medicine. 381, 17, p. 1621-1631 11 p.

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

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DOI

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

BackgroundIt is unknown whether patients undergoing primary percutaneous coronary intervention (PCI) benefit from genotype-guided selection of oral P2Y(12) inhibitors.

MethodsWe 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) 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).

ResultsFor 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

ConclusionsIn 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.)

Patients undergoing primary PCI were randomly assigned to either a genotype-guided strategy for selecting a P2Y(12) inhibitor or to standard treatment with ticagrelor or prasugrel. At 12 months, genotype-guided therapy was noninferior to standard treatment with respect to thrombotic events and resulted in a lower incidence of bleeding.

Original languageEnglish
Pages (from-to)1621-1631
Number of pages11
JournalNew England Journal of Medicine
Volume381
Issue number17
Early online date3-Sep-2019
Publication statusPublished - 24-Oct-2019

    Keywords

  • PERCUTANEOUS CORONARY INTERVENTION, ELEVATION MYOCARDIAL-INFARCTION, DUAL ANTIPLATELET THERAPY, ST-SEGMENT ELEVATION, CYP2C19 GENOTYPE, STENT THROMBOSIS, OPEN-LABEL, CLOPIDOGREL, OUTCOMES, MULTICENTER

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