A Genotype-Guided Strategy for Oral P2Y(12) Inhibitors in Primary PCIClaassens, 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.
Research output: Contribution to journal › Article › Academic › peer-review
- Cardiovascular Centre (CVC)
- Value, Affordability and Sustainability (VALUE)
- Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
- Microbes in Health and Disease (MHD)
- PharmacoTherapy, Epidemiology and Economics
- Methods in Medicines evaluation & Outcomes research (M2O)
- Pharmacoepidemiology and Pharmacoeconomics
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.
|Number of pages||11|
|Journal||New England Journal of Medicine|
|Early online date||3-Sep-2019|
|Publication status||Published - 24-Oct-2019|
- PERCUTANEOUS CORONARY INTERVENTION, ELEVATION MYOCARDIAL-INFARCTION, DUAL ANTIPLATELET THERAPY, ST-SEGMENT ELEVATION, CYP2C19 GENOTYPE, STENT THROMBOSIS, OPEN-LABEL, CLOPIDOGREL, OUTCOMES, MULTICENTER