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Am Heart J. 2014 Jul;168(1):16-22.e1. doi: 10.1016/j.ahj.2014.03.006. Epub 2014 Mar 21.

CYP2C19 genotype-guided antiplatelet therapy in ST-segment elevation myocardial infarction patients-Rationale and design of the Patient Outcome after primary PCI (POPular) Genetics study.

Author information

1
Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands. Electronic address: jurtenberg@gmail.com.
2
Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands.
3
Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
4
Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands; Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
5
Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht, The Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands; Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom.
6
Department of Cardiology, Isala Klinieken, Zwolle, The Netherlands.
7
Department of Cardiology, Amphia Hospital, Breda, The Netherlands.
8
Department of Cardiology, Meander Medical Center, Amersfoort, The Netherlands.
9
Department of Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
10
Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
11
Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
12
Department of Clinical Pharmacy, St Antonius Hospital, Nieuwegein, The Netherlands.

Abstract

RATIONALE:

In patients with ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (pPCI), the use of dual antiplatelet therapy is essential to prevent atherothrombotic complications. Therefore, patients are treated with acetylsalicylic acid and clopidogrel, prasugrel, or ticagrelor. Clopidogrel, however, shows a major interindividual variation in antiplatelet effect, which is correlated to an increase in atherothrombotic events in patients with high platelet reactivity. This interindividual variation is partly a result of CYP2C19 genetic variants. Ticagrelor and prasugrel reduce atherothrombotic events but increase bleeding rate and drug costs, as compared with clopidogrel. CYP2C19-based tailoring of antiplatelet therapy might be beneficial to STEMI patients.

STUDY DESIGN:

POPular Genetics (NCT01761786) is a randomized, open-label, multicenter trial involving 2,700 STEMI patients who undergo pPCI. Patients are randomized to CYP2C19 genotyping or routine ticagrelor or prasugrel treatment. In the genotyping group, *1/*1 (wild-type) patients receive clopidogrel, and patients carrying 1 or 2 *2 or *3 loss-of-function alleles receive ticagrelor or prasugrel. The primary net clinical benefit end point is the composite of death, (recurrent) myocardial infarction, definite stent thrombosis, stroke, and Platelet Inhibition and Patient Outcomes (PLATO) major bleeding at 1 year. Primary safety end point is the composite of (PLATO) major and minor bleeding. Cost-effectiveness and quality of life will be assessed by calculating quality-adjusted life-years, net costs per life-year, and per quality-adjusted life-year gained.

CONCLUSION:

The POPular Genetics study is the first large-scale trial comparing CYP2C19 genotype-guided antiplatelet therapy to a nontailored strategy in terms of net clinical benefit, safety, and cost-effectiveness.

PMID:
24952855
DOI:
10.1016/j.ahj.2014.03.006
[Indexed for MEDLINE]
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