title: Tailored Thienopyridine therapy: no urgency for CYP2C19 genotyping.
abstract: Between 20% and 50% of cardiovascular patients treated with clopidogrel, an anti-P2Y12 drug, display high on-treatment platelet reactivity (HTPR) and are not adequately protected from major adverse cardiovascular events (MACE). Despite a minor influence of the CYP2C19*2 genetic variant on the pharmacodynamic response to clopidogrel (5% to 12%) and a limited or absent value for predicting stent thrombosis and MACE, this latter polymorphism is currently considered an important candidate to tailor anti-P2Y12 therapy during percutaneous coronary intervention. Seven studies have examined the value of CYP2C19*2 for predicting HTPR in comparison to a specific pharmacodynamic assay (VASP assay). Overall, the summarized sensitivity of the CYP2C19*2 genotype for predicting HTPR was 37.6% (95% CI: 32.2 to 43.3%), yielding a negative likelihood ratio of only 0.77 (95% CI: 0.68 to 0.86) which confirms its limited value as a routine clinical aid. A tailored anti-P2Y12 treatment strategy restricted to CYP2C19*2 carriers may be of some help, but this restrictive approach leaves out noncarriers with HTPR. As for platelet function testing, there is currently no convincing data to support that using CYP2C19*2 genotyping as a tailored anti-P2Y12 treatment would be an effective strategy and there is no urgency for CYP2C19 genotyping in clinical practice. Strategies incorporating genotyping, phenotyping, and clinical data in a stratified and sequential approach may be more promising.
authors.affiliation: Division of Angiology and Haemostasis, Geneva University Hospital and Faculty of Medicine.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fontana
authors.forename: Marco
authors.initials: M
authors.lastname: Cattaneo
authors.forename: Christophe
authors.initials: C
authors.lastname: Combescure
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Reny
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D060005:Genotyping Techniques / Q000706:statistics & numerical data; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods; D011110:Polymorphism, Genetic; D057285:Precision Medicine / Q000592:standards; D058921:Purinergic P2Y Receptor Antagonists / Q000493:pharmacokinetics* / Q000627:therapeutic use; D058924:Thienopyridines / Q000493:pharmacokinetics / Q000627:therapeutic use; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D058924:Thienopyridines; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
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