title: Physician response to implementation of genotype-tailored antiplatelet therapy.
abstract: Physician responses to genomic information are vital to the success of precision medicine initiatives. We prospectively studied a pharmacogenomics implementation program for the propensity of clinicians to select antiplatelet therapy based on CYP2C19 loss-of-function variants in stented patients. Among 2,676 patients, 514 (19.2%) were found to have a CYP2C19 variant affecting clopidogrel metabolism. For the majority (93.6%) of the cohort, cardiologists received active and direct notification of CYP2C19 status. Over 12 months, 57.6% of poor metabolizers and 33.2% of intermediate metabolizers received alternatives to clopidogrel. CYP2C19 variant status was the most influential factor impacting the prescribing decision (hazard ratio [HR] in poor metabolizers 8.1, 95% confidence interval [CI] [5.4, 12.2] and HR 5.0, 95% CI [4.0, 6.3] in intermediate metabolizers), followed by patient age and type of stent implanted. We conclude that cardiologists tailored antiplatelet therapy for a minority of patients with a CYP2C19 variant and considered both genomic and nongenomic risks in their clinical decision-making.
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Peterson
authors.affiliation: Institute of Clinical and Translational Research, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Field
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Unertl
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Schildcrout
authors.affiliation: Department of Pharmacy, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Johnson
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Institute of Clinical and Translational Research, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: I
authors.initials: I
authors.lastname: Danciu
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Cleator
authors.affiliation: Institute of Clinical and Translational Research, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Pulley
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: McPherson
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Denny
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: M
authors.initials: M
authors.lastname: Laposata
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Roden
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: K B
authors.initials: KB
authors.lastname: Johnson
mesh_terms: D000367:Age Factors; D000368:Aged; D000066491:Clinical Decision-Making; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data*; D057285:Precision Medicine / Q000379:methods; D011446:Prospective Studies; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine