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

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; Jurriën M Ten Berg

doi:10.1056/NEJMoa1907096

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

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, Jurriën M Ten Berg

Research output: Contribution to journal › Article › Academic › peer-review

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; Netherlands Trial Register number, NL2872.).

Original language	English
Pages (from-to)	1621-1631
Number of pages	11
Journal	New England Journal of Medicine
Volume	381
DOIs	https://doi.org/10.1056/NEJMoa1907096
Publication status	Published - 24 Oct 2019

Access to Document

10.1056/NEJMoa1907096

nejmoa1907096Final published version, 338 KBLicence: Taverne

Cite this

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., Tjon Joe Gin, R. M., 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. (2019). A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI. New England Journal of Medicine, 381, 1621-1631. https://doi.org/10.1056/NEJMoa1907096

@article{794e21291eb047f98088b6d2d53b1093,

title = "A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI",

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; Netherlands Trial Register number, NL2872.).",

author = "Claassens, {Daniel M F} and Vos, {Gerrit J A} and Bergmeijer, {Thomas O} and Hermanides, {Renicus S} and {van 't Hof}, {Arnoud W J} and {van der Harst}, Pim and Emanuele Barbato and Carmine Morisco and {Tjon Joe Gin}, {Richard M} and Asselbergs, {Folkert W} and Arend Mosterd and Herrman, {Jean-Paul R} and Dewilde, {Willem J M} and Janssen, {Paul W A} and Kelder, {Johannes C} and Postma, {Maarten J} and {de Boer}, Anthonius and Cornelis Boersma and Deneer, {Vera H M} and {Ten Berg}, {Jurri{\"e}n M}",

note = "Copyright {\textcopyright} 2019 Massachusetts Medical Society.",

year = "2019",

month = oct,

day = "24",

doi = "10.1056/NEJMoa1907096",

language = "English",

volume = "381",

pages = "1621--1631",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

}

Claassens, DMF, Vos, GJA, Bergmeijer, TO, Hermanides, RS, van 't Hof, AWJ, van der Harst, P, Barbato, E, Morisco, C, Tjon Joe Gin, RM, Asselbergs, FW, Mosterd, A, Herrman, J-PR, Dewilde, WJM, Janssen, PWA, Kelder, JC, Postma, MJ, de Boer, A, Boersma, C, Deneer, VHM & Ten Berg, JM 2019, 'A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI', New England Journal of Medicine, vol. 381, pp. 1621-1631. https://doi.org/10.1056/NEJMoa1907096

TY - JOUR

T1 - A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI

AU - Claassens, Daniel M F

AU - Vos, Gerrit J A

AU - Bergmeijer, Thomas O

AU - Hermanides, Renicus S

AU - van 't Hof, Arnoud W J

AU - van der Harst, Pim

AU - Barbato, Emanuele

AU - Morisco, Carmine

AU - Tjon Joe Gin, Richard M

AU - Asselbergs, Folkert W

AU - Mosterd, Arend

AU - Herrman, Jean-Paul R

AU - Dewilde, Willem J M

AU - Janssen, Paul W A

AU - Kelder, Johannes C

AU - Postma, Maarten J

AU - de Boer, Anthonius

AU - Boersma, Cornelis

AU - Deneer, Vera H M

AU - Ten Berg, Jurriën M

PY - 2019/10/24

Y1 - 2019/10/24

N2 - 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.).

AB - 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.).

U2 - 10.1056/NEJMoa1907096

DO - 10.1056/NEJMoa1907096

M3 - Article

C2 - 31479209

SN - 0028-4793

VL - 381

SP - 1621

EP - 1631

JO - New England Journal of Medicine

JF - New England Journal of Medicine

ER -

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

Abstract

Access to Document

Fingerprint

Cite this