TY - JOUR
T1 - A Genotype-Guided Strategy for Oral P2Y(12) 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 - Gin, Richard M. Tjon Joe
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, Jurrien M.
N1 - Copyright © 2019 Massachusetts Medical Society.
PY - 2019/10/24
Y1 - 2019/10/24
N2 - 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; PConclusionsIn 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.
AB - 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; PConclusionsIn 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.
KW - PERCUTANEOUS CORONARY INTERVENTION
KW - ELEVATION MYOCARDIAL-INFARCTION
KW - DUAL ANTIPLATELET THERAPY
KW - ST-SEGMENT ELEVATION
KW - CYP2C19 GENOTYPE
KW - STENT THROMBOSIS
KW - OPEN-LABEL
KW - CLOPIDOGREL
KW - OUTCOMES
KW - MULTICENTER
U2 - 10.1056/NEJMoa1907096
DO - 10.1056/NEJMoa1907096
M3 - Article
C2 - 31479209
VL - 381
SP - 1621
EP - 1631
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 17
ER -