Faculty Collaboration Database

Prospective CYP2C19 Genotyping to Guide Antiplatelet Therapy Following Percutaneous Coronary Intervention: A Pragmatic Randomized Clinical Trial. Circ Genom Precis Med 2020 Feb;13(1):e002640

Date

01/14/2020

Pubmed ID

31928229

DOI

10.1161/CIRCGEN.119.002640

Scopus ID

2-s2.0-85080846349 (requires institutional sign-in at Scopus site)   39 Citations

Abstract

BACKGROUND: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after percutaneous coronary intervention, but the clinical impact of implementing CYP2C19 genotyping in a real-world setting is unknown. The purpose of the study was to determine whether returning CYP2C19 genotype results along with genotype-guided pharmacotherapy recommendations using a rapid turnaround test would change antiplatelet prescribing following percutaneous coronary intervention.The primary outcome was the rate of prasugrel or ticagrelor prescribing in each arm. Secondary outcomes included agreement to the genotype-guided recommendations.

METHODS: At the time of percutaneous coronary intervention, participants were randomly assigned to prospective rapid point-of-care genotyping of CYP2C19 major alleles (*2, *3, *17) via salivary swab (genotyped group) or no genotyping (usual care) to guide antiplatelet drug selection. Interventional cardiologists at 2 cardiac catheterization laboratories within the same health system were provided genotype information along with genotype-guided pharmacotherapy recommendations.

RESULTS: A total of 504 participants were randomized, 249 to the genotyped and 255 to the usual care group. The participants were primarily men (73%); age, 63±10 years; and 50% had acute coronary syndromes. In the genotyped group, 28% were carriers of loss-of-function alleles (*2, *3). The use of prasugrel or ticagrelor was significantly higher in the genotyped group compared with the usual care group (30% versus 21%; odds ratio, 1.60 [95% CI, 1.07-2.42]; P=0.03). Within the genotyped group, 53% of loss-of-function allele carriers were started on prasugrel/ticagrelor, while 47% were started on clopidogrel.

CONCLUSIONS: In a randomized controlled trial of clinical CYP2C19 genotyping implementation, pharmacogenetic test results significantly influenced antiplatelet drug prescribing; however, almost half of CYP2C19 loss-of-function carriers continued to receive clopidogrel. Interventional cardiologists consider both clinical and genetic factors when selecting antiplatelet therapy following percutaneous coronary intervention.

CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT02508116.

Author List

Tuteja S, Glick H, Matthai W, Nachamkin I, Nathan A, Monono K, Carcuffe C, Maslowski K, Chang G, Kobayashi T, Anwaruddin S, Hirshfeld J, Wilensky RL, Herrmann HC, Kolansky DM, Rader DJ, Giri J

Author

Saif Anwaruddin MD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Coronary Syndrome
Biomarkers
Cytochrome P-450 CYP2C19
Female
Follow-Up Studies
Genotype
Humans
Male
Middle Aged
Percutaneous Coronary Intervention
Pharmacogenomic Testing
Platelet Aggregation Inhibitors
Polymorphism, Genetic
Prognosis
Prospective Studies