title: Impact of point-of-care testing for CYP2C19 on platelet inhibition in patients with acute coronary syndrome and early dual antiplatelet therapy in the emergency setting.
abstract: OBJECTIVE
  Only limited data exist about the role of point of care CYP2C19 testing in the acute setting in the early phase of acute coronary syndromes (ACS). Therefore, the present study was designed to investigate the impact of CYP2C19 loss-of-function point-of-care (POC) genotyping in patients presenting with acute coronary syndromes (ACS) and treated with dual antiplatelet therapy in the emergency setting.
  
  
  RESULTS
  137 subjects with ACS scheduled for percutaneous coronary intervention were consecutively enrolled. Pre- and on-treatment platelet aggregation was assessed by multiple electrode aggregometry (MEA) after stimulation with adenosine diphosphate (ADP). Patients were loaded according to current guideline adherent indications and contraindications for use of P2Y12 inhibitors in ACS. POC genotyping for CYP2C19*2 was performed in the emergency room after obtaining a buccal swab using the Spartan RX CYP2C19 system and obtaining patient's informed consent. Prasugrel and ticagrelor treated patients had significantly lower PR compared to clopidogrel-treated patients. The benefits of prasugrel and ticagrelor compared to clopidogrel treated patients in terms of platelet inhibition were more pronounced in CYP2C19*2 carriers. Non-carriers showed similar inhibition regardless of particular P2Y12 inhibitor treatment. Statistical analyses adjusting for factors associated with response (e.g. smoking) revealed that CYP2C19*2 allele carrier status and loading with different type of P2Y12 receptor blockers were significant predictors of on-treatment platelet reactivity in the early phase of ACS.
  
  
  CONCLUSIONS
  The results of this pilot study of treatment of patients in the early phase of ACS indicate that CYP2C19*2 POC genotyping might help to identify patients at risk with poor response to clopidogrel treatment, thereby benefiting from reloading and switching to alternative P2Y12 receptor inhibition.
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Stimpfle
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Karathanos
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Michal
authors.initials: M
authors.lastname: Droppa
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Metzger
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Rath
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Müller
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Elli
authors.initials: E
authors.lastname: Tavlaki
authors.affiliation: Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany; University Tübingen, Tübingen, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Schäffeler
authors.affiliation: Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany; University Tübingen, Tübingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Winter
authors.affiliation: Department of Clinical Pharmacology, University Hospital of Tübingen, Tübingen, Germany; Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University Hospital of Tübingen, Tübingen, Germany.
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.affiliation: Department of Cardiology and Cardiovascular Medicine, University Hospital of Tübingen, Tübingen, Germany. Electronic address: tobias.geisler@med.uni-tuebingen.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Geisler
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology*; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D065731:Cytochrome P-450 CYP2C19 / Q000032:analysis / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D010865:Pilot Projects; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019095:Point-of-Care Systems; D000068799:Prasugrel Hydrochloride; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*; D000077486:Ticagrelor
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine; D001241:Aspirin
keywords: Acute coronary syndrome; CYP2C19; Clopidogrel; Pharmacogenetics; Prasugrel; Ticagrelor