Genotype-guided antiplatelet therapy is increasingly being incorporated into clinical care. The purpose of this study is to determine the extent to which patients initially genotyped for CYP2C19 to guide antiplatelet therapy were prescribed additional medications affected by CYP2C19.
We assembled a cohort of patients from eight sites performingCYP2C19 genotyping to inform antiplatelet therapy. Medication orders were evaluated from time of genotyping through one year. The primary endpoint was the proportion of patients prescribed two or more CYP2C19 substrates. Secondary endpoints were the proportion of patients with a drug–genotype interaction and time to receiving a CYP2C19 substrate.
Nine thousand one hundred ninety-one genotyped patients (17% nonwhite) with a mean age of 68 ± 3 years were evaluated; 4701 (51%) of patients received two or more CYP2C19 substrates and 3835 (42%) of patients had a drug–genotype interaction. The average time between genotyping and CYP2C19 substrate other than antiplatelet therapy was 25 ± 10 days.
More than half of patients genotyped in the setting of CYP2C19-guided antiplatelet therapy received another medication impacted by CYP2C19 in the following year. Given that genotype is stable for a patient’s lifetime, this finding has implications for cost effectiveness, patient care, and treatment outcomes beyond the indication for which it was originally performed.
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Empey PE, Stevenson JM, Tuteja S, et al. Multisite investigation of strategies for the implementation of CYP2C19 genotype-guided antiplatelet therapy. Clin Pharmacol Ther. 2018;104:664–674.
Limdi NA, Cavallari LH, Lee CR, et al. Cost-effectiveness of CYP2C19-guided antiplatelet therapy in patients with acute coronary syndrome and percutaneous coronary intervention informed by real world data. Pharmacogenomics J. 2020 Feb 11; https://doi.org/10.1038/s41397-020-0162-5 [Epub ahead of print].
Reese ES, Daniel Mullins C, Beitelshees AL, Onukwugha E. Cost-effectiveness of cytochrome P450 2C19 genotype screening for selection of antiplatelet therapy with clopidogrel or prasugrel. Pharmacotherapy. 2012;32:323–332.
Sorich MJ, Horowitz JD, Sorich W, Wiese MD, Pekarsky B, Karnon JD. Cost-effectiveness of using CYP2C19 genotype to guide selection of clopidogrel or ticagrelor in Australia. Pharmacogenomics. 2013;14:2013–2021.
Scott SA, Sangkuhl K, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther. 2013;94:317–323.
Mega JL, Close SL, Wiviott SD, et al. Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis. Lancet. 2010;376:1312–1319.
Mega JL, Simon T, Collet JP, et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 2010;304:1821–1830.
Osnabrugge RL, Kappetein AP, Janssens AC. Carriage of reduced-function CYP2C19 allele among patients treated with clopidogrel. JAMA. 2011;305:467–468.
Claassens DMF, Vos GJA, Bergmeijer TO, et al. A genotype-guided strategy for oral P2Y12 inhibitors in primary PCI. N Engl J Med. 2019;381:1621–1631.
Hicks JK, Bishop JR, Sangkuhl K, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther. 2015;98:127–134.
Hicks JK, Sangkuhl K, Swen JJ, et al. Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther. 2017;102:37–44.
Moriyama B, Obeng AO, Barbarino J, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP2C19 and voriconazole therapy. Clin Pharmacol Ther. 2017;102:45–51.
Cavallari LH, Lee CR, Beitelshees AL, et al. Multisite investigation of outcomes with implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention. JACC Cardiovasc Interv. 2018;11:181–191.
US Food and Drug Adminnistration. The FDA warns against the use of many genetic tests with unapproved claims to predict patient response to specific medications: FDA safety communication. 2018. https://www.fda.gov/medical-devices/safety-communications/fda-warns-against-use-many-genetic-tests-unapproved-claims-predict-patient-response-specific. Accessed 18 December 2019.
US Food and Drug Administration. FDA issues warning letter to genomics lab for illegally marketing genetic test that claims to predict patients’ responses to specific medications. 2019. https://www.fda.gov/news-events/press-announcements/fda-issues-warning-letter-genomics-lab-illegally-marketing-genetic-test-claims-predict-patients. Accessed 18 December 2019.
Carere DA, VanderWeele TJ, Vassy JL, et al. Prescription medication changes following direct-to-consumer personal genomic testing: findings from the Impact of Personal Genomics (PGen) Study. Genet Med. 2017;19:537–545.
GenomeWeb. New coalition, stakeholder groups push back against FDA ‘backdoor' attempts to regulate PGx tests. 2019. https://www.genomeweb.com/molecular-diagnostics/new-coalition-stakeholder-groups-push-back-against-fda-backdoor-attempts#.XfpZbvx7mUk. Accessed 18 December 2019.
Haidar CE, Relling MV, Hoffman JM. Preemptively precise: returning and updating pharmacogenetic test results to realize the benefits of preemptive testing. Clin Pharmacol Ther. 2019;106:942–944.
Funding for this work was provided by National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI) U01HG007775 (A.L.B.); American Heart Association 17MCPRP33400175 (J.M.S.); National Heart, Lung, and Blood Institute (NHLBI) K23HL143161 and Penn Center for Precision Medicine (S.T.); RO1HL092173 and K24HL133373, Clinical and Translational Science Award UL1TR000165, University of Alabama Birmingham’s Health Service Foundations’ General Endowment Fund and Hugh Kaul Personalized Medicine Institute (N.A.L., C.D.); the American Society of Health System Pharmacists, NIH UL1TR0000005, and by an Anonymous Donor (J.M.S. and P.E.E.), NIH/NHGRI U01HG007253 and U01HG010232 (J.F.P. and E.M.F.), NIH NHGRI U01 HG007269 and NIH National Center for Advancing Translational Sciences (NCATS) UL1 TR000064 (J.A.J. and L.H.C.).
J.F.P. is a consultant for Color Genomics. T.C.S. is paid as a pharmacogenetics consultant for IU Health. D.J.A. declares that he has received consulting fees or honoraria from Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company and has received payments for participation in review activities from CeloNova and St Jude Medical. D.J.A. also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, Renal Guard Solutions, and Scott R. MacKenzie Foundation. F.F. declares that he has received consulting fees or honoraria from, AstraZeneca, Bayer, Sanofi. The other authors declare no conflicts of interest.
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Beitelshees, A.L., Stevenson, J.M., El Rouby, N. et al. Evaluating the extent of reusability of CYP2C19 genotype data among patients genotyped for antiplatelet therapy selection. Genet Med (2020). https://doi.org/10.1038/s41436-020-0894-2