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.
N1 - 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.
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 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 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.).
AB - 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 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.).
KW - Administration, Oral
KW - Aged
KW - Clopidogrel/adverse effects
KW - Coronary Thrombosis/prevention & control
KW - Cytochrome P-450 CYP2C19/genetics
KW - Female
KW - Genotype
KW - Hemorrhage/chemically induced
KW - Humans
KW - Intention to Treat Analysis
KW - Male
KW - Middle Aged
KW - Percutaneous Coronary Intervention
KW - Prasugrel Hydrochloride/adverse effects
KW - Precision Medicine
KW - Purinergic P2Y Receptor Antagonists/adverse effects
KW - ST Elevation Myocardial Infarction/drug therapy
KW - Single-Blind Method
KW - Stents
KW - Ticagrelor/adverse effects
UR - https://www.scopus.com/pages/publications/85073605842
U2 - 10.1056/NEJMoa1907096
DO - 10.1056/NEJMoa1907096
M3 - Article
C2 - 31479209
AN - SCOPUS:85073605842
SN - 0028-4793
VL - 381
SP - 1621
EP - 1631
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 17
ER -