Relling MV, Evans WE. Pharmacogenomics in the clinic. Nature. 2015;526(7573):343–50.

Article  Google Scholar 

Nussbaum RL. Thompson & Thompson genetics in medicine. In: McInnes RR, Willard HF, editors. 8th ed.

Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998;279(15):1200–5.

Article  Google Scholar 

Gandhi TK, Weingart SN, Borus J, Seger AC, Peterson J, Burdick E, et al. Adverse drug events in ambulatory care. N Engl J Med. 2003;348(16):1556–64.

Article  Google Scholar 

Spear BB, Heath-Chiozzi M, Huff J. Clinical application of pharmacogenetics. Trends Mol Med. 2001;7(5):201–4.

Article  Google Scholar 

Watanabe JH, McInnis T, Hirsch JD. Cost of prescription drug-related morbidity and mortality. Ann Pharmacother. 2018;52(9):829–37.

Article  Google Scholar 

Bush WS, Crosslin DR, Obeng AO, Wallace J, Almoguera B, Basford MA, et al. Genetic variation among 82 pharmacogenes: the PGRN-Seq data from the eMERGE Network. Clin Pharmacol Ther. 2016;100(2):160–9.

Van Driest SL, Shi Y, Bowton EA, Schildcrout JS, Peterson JF, Pulley J, et al. Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing. Clin Pharmacol Ther. 2014;95(4):423–31.

Article  Google Scholar 

Chanfreau-Coffinier C, Hull LE, Lynch JA, DuVall SL, Damrauer SM, Cunningham FE, et al. Projected prevalence of actionable pharmacogenetic variants and level a drugs prescribed among US veterans health administration pharmacy users. JAMA Netw Open. 2019;2(6):e195345.

Article  Google Scholar 

McInnes G, Lavertu A, Sangkuhl K, Klein TE, Whirl-Carrillo M, Altman RB. Pharmacogenetics at scale: an analysis of the UK Biobank. Clin Pharmacol Ther. 2021;109(6):1528–37.

Article  Google Scholar 

Drozda K, Pacanowski MA, Grimstein C, Zineh I. Pharmacogenetic labeling of FDA-approved drugs: a regulatory retrospective. JACC Basic Transl Sci. 2018;3(4):545–9.

Article  Google Scholar 

CPIC: Clinical pharmacogenetics implementation consortium. https://cpicpgx.org/ (accessed March 8, 2016).

Scott SA, Sangkuhl K, Gardner EE, Stein CM, Hulot JS, Johnson JA, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450–2C19 (CYP2C19) genotype and clopidogrel therapy. Clin Pharmacol Ther. 2011;90(2):328–32.

Article  Google Scholar 

Johnson JA, Gong L, Whirl-Carrillo M, Gage BF, Scott SA, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 Genotypes and Warfarin Dosing. Clin Pharmacol Ther. 2011;90(4):625–9.

Article  Google Scholar 

Lee CR, Luzum JA, Sangkuhl K, Gammal RS, Sabatine MS, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy: 2022 Update. Clin Pharmacol Ther. 2022;112(5):959–67.

Johnson JA, Caudle KE, Gong L, Whirl-Carrillo M, Stein CM, Scott SA, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update. Clin Pharmacol Ther. 2017;102(3):397–404.

Article  Google Scholar 

Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. Circulation. 2016;134(10):e123–55.

Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58(24):e44–122.

Franchi F, Angiolillo DJ. Novel antiplatelet agents in acute coronary syndrome. Nat Rev Cardiol. 2015;12(1):30–47.

Article  Google Scholar 

Brandt JT, Close SL, Iturria SJ, Payne CD, Farid NA, Ernest CS 2nd, et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J Thromb Haemost JTH. 2007;5(12):2429–36.

Article  Google Scholar 

Gurbel PA, Bergmeijer TO, Tantry US, ten Berg JM, Angiolillo DJ, James S, et al. The effect of CYP2C19 gene polymorphisms on the pharmacokinetics and pharmacodynamics of prasugrel 5-mg, prasugrel 10-mg and clopidogrel 75-mg in patients with coronary artery disease. Thromb Haemost. 2014;112(3):589–97.

Google Scholar 

Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001–15.

Article  Google Scholar 

Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045–57.

Article  Google Scholar 

Dayoub EJ, Seigerman M, Tuteja S, Kobayashi T, Kolansky DM, Giri J, et al. Trends in platelet adenosine diphosphate P2Y12 receptor inhibitor use and adherence among antiplatelet-naive patients after percutaneous coronary intervention, 2008–2016. JAMA Intern Med. 2018;178(7):943–50.

Article  Google Scholar 

Dayoub EJ, Nathan AS, Khatana SAM, Seigerman M, Tuteja S, Kobayashi T, et al. Use of prasugrel and ticagrelor in stable ischemic heart disease after percutaneous coronary intervention, 2009–2016. Circ Cardiovasc Interv. 2019;12(1):e007434.

Article  Google Scholar 

Karve AM, Seth M, Sharma M, LaLonde T, Dixon S, Wohns D, et al. Contemporary use of ticagrelor in interventional practice (from Blue Cross Blue Shield of Michigan Cardiovascular Consortium). Am J Cardiol. 2015;115(11):1502–6.

Article  Google Scholar 

Kazui M, Nishiya Y, Ishizuka T, Hagihara K, Farid NA, Okazaki O, et al. Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos. 2010;38(1):92–9.

Article  Google Scholar 

Sibbing D, Aradi D, Alexopoulos D, ten Berg J, Bhatt DL, Bonello L, et al. Updated Expert Consensus Statement on Platelet Function and Genetic Testing for Guiding P2Y12 Receptor Inhibitor Treatment in Percutaneous Coronary Intervention. JACC Cardiovasc Interv. 2019;12(16):1521–37.

Sibbing D, Koch W, Gebhard D, Schuster T, Braun S, Stegherr J, et al. Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation. 2010;121(4):512–8.

Article  Google Scholar 

Pereira NL, Rihal CS, So DYF, Rosenberg Y, Lennon RJ, Mathew V, et al. Clopidogrel pharmacogenetics. Circ Cardiovasc Interv. 2019;12(4):e007811.

Article  Google Scholar 

Shuldiner AR, O’Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009;302(8):849–57.

Article  Google Scholar 

Lewis JP, Backman JD, Reny JL, Bergmeijer TO, Mitchell BD, Ritchie MD, et al. Pharmacogenomic polygenic response score predicts ischemic events and cardiovascular mortality in clopidogrel-treated patients. Eur Heart J Cardiovasc Pharmacother. 2020;6(4):203–10.

Lewis JP, Stephens SH, Horenstein RB, O’Connell JR, Ryan K, Peer CJ, et al. The CYP2C19*17 variant is not independently associated with clopidogrel response. J Thromb Haemost JTH. 2013;11(9):1640–6.

Article  Google Scholar 

Lee CR, Thomas CD, Beitelshees AL, Tuteja S, Empey PE, Lee JC, et al. Impact of the CYP2C19*17 allele on outcomes in patients receiving genotype-guided antiplatelet therapy after percutaneous coronary intervention. Clin Pharmacol Ther. 2021;109(3):705–15.

Mega JL, Simon T, Collet JP, Anderson JL, Antman EM, Bliden K, 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(16):1821–30.

Article  Google Scholar 

Cavallari LH, Lee CR, Beitelshees AL, Cooper-DeHoff RM, Duarte JD, Voora D, et al. Multisite investigation of outcomes with implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention. JACC Cardiovasc Interve. 2017.

Shen DL, Wang B, Bai J, Han Q, Liu C, Huang XH, et al. Clinical value of CYP2C19 genetic testing for guiding the antiplatelet therapy in a Chinese population. J Cardiovasc Pharmacol. 2016;67(3):232–6.

Article  Google Scholar 

Hulot JS, Chevalier B, Belle L, Cayla G, Khalife K, Funck F, et al. Routine CYP2C19 genotyping to adjust thienopyridine treatment after primary PCI for STEMI: results of the GIANT study. JACC Cardiovasc Interv. 2020;13(5):621–30.

Article  Google Scholar 

Beitelshees AL, Thomas CD, Empey PE, Stouffer GA, Angiolillo DJ, Franchi F, et al. CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention in diverse clinical settings. J Am Heart Assoc. 2022;11(4):e024159.

Article  Google Scholar 

Claassens DMF, Vos GJA, Bergmeijer TO, Hermanides RS, van’t Hof AWJ, van der Harst P, et al. A genotype-guided strategy for oral P2Y12 inhibitors in primary PCI. N Engl J Med. 2019;381(17):1621–31.

Pereira NL, Farkouh ME, So D, Lennon R, Geller N, Mathew V, et al. Effect of genotype-guided oral P2Y12 inhibitor selection vs conventional clopidogrel therapy on ischemic outcomes after percutaneous coronary intervention: the TAILOR-PCI randomized clinical trial. JAMA. 2020;324(8):761–71.

Article  Google Scholar 

Notarangelo FM, Maglietta G, Bevilacqua P, Cereda M, Merlini PA, Villani GQ, et al. Pharmacogenomic approach to selecting antiplatelet therapy in patients with acute coronary syndromes: the PHARMCLO trial. J Am Coll Cardiol. 2018;71(17):1869–77.

Article  Google Scholar 

Zhang Y, Zhao Y, Pang M, Wu Y, Zhuang K, Zhang H, et al. High-dose clopidogrel versus ticagrelor for treatment of acute coronary syndromes after percutaneous coronary intervention in CYP2C19 intermediate or poor metabolizers: a prospective, randomized, open-label, single-centre trial. Acta Cardiol. 2016;71(3):309–16.

Article  Google Scholar 

Ogawa H, Isshiki T, Kimura T, Yokoi H, Nanto S, Takayama M, et al. Effects of CYP2C19 allelic variants on inhibition of platelet aggregation and major adverse cardiovascular events in Japanese patients with acute coronary syndrome: The PRASFIT-ACS study. J Cardiol. 2016;68(1):29–36.

Article  Google Scholar 

Tuteja S, Glick H, Matthai W, Nachamkin I, Nathan A, Monono K, et al. Prospective CYP2C19 genotyping to guide antiplatelet therapy following percutaneous coronary intervention: a pragmatic randomized clinical trial. Circ Genom Precis Med. 2020;13(1):e002640.

Article  Google Scholar 

Sánchez-Ramos J, Dávila-Fajardo CL, Toledo Frías P, Díaz Villamarín X, Martínez-González LJ, Martínez Huertas S, et al. Results of genotype-guided antiplatelet therapy in patients who undergone percutaneous coronary intervention with stent. Int J Cardiol. 2016;225:289–95.

Article  Google Scholar 

Lee CR, Sriramoju VB, Cervantes A, Howell LA, Varunok N, Madan S, et al. Clinical outcomes and sustainability of using CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention. Circ Genom Precis Med. 2018;11(4):e002069.

Article  Google Scholar 

Wang Y, Wang Y, Zhao X, Liu L, Wang D, Wang C, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369(1):11–9.

Article  Google Scholar 

Pan Y, Chen W, Xu Y, Yi X, Han Y, Yang Q, et al. Genetic polymorphisms and clopidogrel efficacy for acute ischemic stroke or transient ischemic attack: a systematic review and meta-analysis. Circulation. 2017;135(1):21–33.

Article  Google Scholar 

Wang Y, Meng X, Wang A, Xie X, Pan Y, Johnston SC, et al. Ticagrelor versus clopidogrel in CYP2C19 loss-of-function carriers with stroke or TIA. N Engl J Med. 2021;385(27):2520–30.

Holmes DR Jr, Dehmer GJ, Kaul S, Leifer D, O’Gara PT, Stein CM. ACCF/AHA Clopidogrel clinical alert: approaches to the FDA “boxed warning”: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the American Heart Association. Circulation. 2010;122(5):537–57.

Article  Google Scholar 

US Food and Drug Administration. FDA Drug Safety Communication: reduced effectiveness of Plavix (clopidogrel) in patients who are poor metabolizers of the drug, March 2010. Available at https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-reduced-effectiveness-plavix-clopidogrel-patients-who-are-poor. Accessed 7–20–2022.

Empey PE, Pratt VM, Hoffman JM, Caudle KE, Klein TE. Expanding evidence leads to new pharmacogenomics payer coverage. Genet Med. 2021;23(5):830–2.

Article  Google Scholar 

Pharmacogenomic Testing Local Coverage Determination. Novitas Solutions. December 12, 2021. Available at: https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=39063&ver=11. Accessed 7/20/2022.

Weitzel KW, Elsey AR, Langaee TY, Burkley B, Nessl DR, Obeng AO, et al. Clinical pharmacogenetics implementation: approaches, successes, and challenges. Am J Med Genet C Semin Med Genet. 2014;166c(1):56–67.

Empey PE, Stevenson JM, Tuteja S, Weitzel KW, Angiolillo DJ, Beitelshees AL, et al. Multisite investigation of strategies for the implementation of CYP2C19 genotype-guided antiplatelet therapy. Clin Pharmacol Ther. 2018;104(4):664–74.

Article  Google Scholar 

Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011;365(21):2002–12.

Article