title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands. Electronic address: jurtenberg@gmail.com.
authors: Thomas O
authors: TO
authors: Bergmeijer
authors: Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands.
authors: Paul W A
authors: PW
authors: Janssen
authors: Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Jurjan C
authors: JC
authors: Schipper
authors: Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands.
authors: Khalid
authors: K
authors: Qaderdan
authors: Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands; Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Maycel
authors: M
authors: Ishak
authors: Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands.
authors: Rianne S
authors: RS
authors: Ruitenbeek
authors: 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.
authors: Folkert W
authors: FW
authors: Asselbergs
authors: Department of Cardiology, Isala Klinieken, Zwolle, The Netherlands.
authors: Arnoud W J
authors: AW
authors: van 't Hof
authors: Department of Cardiology, Amphia Hospital, Breda, The Netherlands.
authors: Willem J M
authors: WJ
authors: Dewilde
authors: Department of Cardiology, Meander Medical Center, Amersfoort, The Netherlands.
authors: Fabrizio
authors: F
authors: Spanó
authors: Department of Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
authors: Jean-Paul R
authors: JP
authors: Herrman
authors: Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands.
authors: Johannes C
authors: JC
authors: Kelder
authors: Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors: Maarten J
authors: MJ
authors: Postma
authors: Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors: Anthonius
authors: A
authors: de Boer
authors: Department of Clinical Pharmacy, St Antonius Hospital, Nieuwegein, The Netherlands.
authors: Vera H M
authors: VH
authors: Deneer
authors: Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands.
authors: Jurriën M
authors: JM
authors: ten Berg
mesh_terms: D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D005821:Genetic Techniques; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011446:Prospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine