{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T19:29:32Z","timestamp":1774380572165,"version":"3.50.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    In the era of precision medicine, dual antiplatelet therapy with aspirin and a\n                    <jats:italic>P2Y12<\/jats:italic>\n                    receptor inhibitor is the standard strategy for patients after percutaneous coronary intervention (PCI). Clopidogrel, as a widely used representative drug, has its efficacy significantly influenced by\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    genetic polymorphisms, leading to poor metabolism in some patients, insufficient exposure to active metabolites, and increased risk of ischemic events. In theory,\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    genotyping to guide individualized antiplatelet therapy could help optimize the clinical selection of\n                    <jats:italic>P2Y12<\/jats:italic>\n                    inhibitors and improve prognosis. However, current evidence and guidelines do not support its use as a routine test for post-PCI patients, reflecting multiple challenges in clinical translation. From the perspective of precision medicine, this article systematically reviews the main problems and clinical application dilemmas of\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    genotyping in guiding clopidogrel therapy, including controversies and uncertainties in randomized controlled trials (RCTs) evidence, neglect of rare alleles, complexity of metabolism regulated by polygenic and clinical factors, and limited predictive value for low platelet reactivity. Finally, this paper prospects future research directions and clinical translation prospects, aiming to provide a theoretical reference for promoting individualized antiplatelet therapy and balancing thrombosis and bleeding risks.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1711350","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T16:10:25Z","timestamp":1774368625000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Challenges and prospects of CYP2C19 genotype-guided clopidogrel therapy from the perspective of precision medicine"],"prefix":"10.3389","volume":"17","author":[{"given":"Zixiao","family":"Wang","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Hebei North University","place":["Zhangjiakou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangkai","family":"Fu","sequence":"additional","affiliation":[{"name":"The First Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cangzhou Central Hospital","place":["Cangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.jcin.2020.01.226","article-title":"Derivation, validation, and prognostic utility of a prediction rule for nonresponse to clopidogrel: the ABCD-GENE score","volume":"13","author":"Angiolillo","year":"2020","journal-title":"JACC Cardiovasc Interv."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2639","DOI":"10.1016\/j.jcin.2024.08.027","article-title":"International Consensus statement on platelet function and genetic testing in percutaneous coronary intervention: 2024 update","volume":"17","author":"Angiolillo","year":"2024","journal-title":"JACC Cardiovasc Interv."},{"key":"B3","doi-asserted-by":"publisher","first-page":"391","DOI":"10.5603\/CJ.a2021.0084","article-title":"Increased risk of adverse events in patients with low-on clopidogrel platelet reactivity after percutaneous coronary intervention: a systematic review and meta-analysis","volume":"30","author":"B\u00e1lint","year":"2023","journal-title":"Cardiol. J."},{"key":"B4","doi-asserted-by":"publisher","first-page":"621","DOI":"10.2217\/pgs-2018-0013","article-title":"Feasibility and implementation of CYP2C19 genotyping in patients using antiplatelet therapy","volume":"19","author":"Bergmeijer","year":"2018","journal-title":"Pharmacogenomics"},{"key":"B5","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1146\/annurev-pharmtox-051921-092701","article-title":"Pharmacogenetics of antiplatelet therapy","volume":"63","author":"Castrichini","year":"2023","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1002\/cpt.70005","article-title":"Advancing clinical pharmacogenomics worldwide through the Clinical Pharmacogenetics Implementation Consortium (CPIC)","volume":"118","author":"Caudle","year":"2025","journal-title":"Clin. Pharmacol. Ther."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1002\/cpt.2055","article-title":"Clopidogrel dosing: current successes and emerging factors for further consideration","volume":"109","author":"Chetty","year":"2021","journal-title":"Clin. Pharmacol. Ther."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1056\/NEJMoa1907096","article-title":"A genotype-guided strategy for oral P2Y(12) inhibitors in primary PCI","volume":"381","author":"Claassens","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1515\/dmpt-2015-0021","article-title":"Pharmacogenetics of healthy volunteers in Puerto Rico","volume":"30","author":"Claudio-Campos","year":"2015","journal-title":"Drug Metab. Pers. Ther."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.2217\/pgs-2016-0056","article-title":"Genetic polymorphisms influence on the response to clopidogrel in peripheral artery disease patients following percutaneous transluminal angioplasty","volume":"17","author":"D\u00edaz-Villamar\u00edn","year":"2016","journal-title":"Pharmacogenomics"},{"key":"B11","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/s41569-021-00549-w","article-title":"Pharmacogenetics to guide cardiovascular drug therapy","volume":"18","author":"Duarte","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1080\/17512433.2021.1927709","article-title":"Genetic testing in patients undergoing percutaneous coronary intervention: rationale, evidence and practical recommendations","volume":"14","author":"Galli","year":"2021","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.tcm.2021.12.007","article-title":"Role of platelet function and genetic testing in patients undergoing percutaneous coronary intervention","volume":"33","author":"Galli","year":"2023","journal-title":"Trends Cardiovasc Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e24855","DOI":"10.1002\/jcla.24855","article-title":"A retrospective analysis of preemptive pharmacogenomic testing in 22,918 individuals from China","volume":"37","author":"Huang","year":"2023","journal-title":"J. Clin. Lab. Anal."},{"key":"B15","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/j.jcin.2020.01.219","article-title":"Routine CYP2C19 genotyping to adjust thienopyridine treatment after primary PCI for STEMI: results of the GIANT Study","volume":"13","author":"Hulot","year":"2020","journal-title":"JACC Cardiovasc Interv."},{"key":"B16","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s40262-014-0230-6","article-title":"Clinical pharmacokinetics and pharmacodynamics of clopidogrel","volume":"54","author":"Jiang","year":"2015","journal-title":"Clin. Pharmacokinet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s40246-025-00765-2","article-title":"Proof of principle concept for the analysis and functional prediction of rare genetic variants in the CYP2C19 and CYP2D6 genes","volume":"19","author":"Johansson","year":"2025","journal-title":"Hum. Genomics"},{"key":"B18","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1002\/ccd.28075","article-title":"Personalized antiplatelet therapy in patients with coronary artery disease undergoing percutaneous coronary intervention: a network meta-analysis of randomized clinical trials","volume":"94","author":"Kheiri","year":"2019","journal-title":"Catheter Cardiovasc Interv."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1002\/cpt.3026","article-title":"High platelet reactivity combined with CYP2C19 genotype in predicting outcomes in East Asian patients undergoing percutaneous coronary intervention","volume":"114","author":"Kim","year":"2023","journal-title":"Clin. Pharmacol. Ther."},{"key":"B20","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/s11883-024-01200-y","article-title":"What causes premature coronary artery disease?","volume":"26","author":"Le","year":"2024","journal-title":"Curr. Atheroscler. Rep."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1080\/17425255.2020.1814254","article-title":"Clopidogrel drug interactions: a review of the evidence and clinical implications","volume":"16","author":"Lee","year":"2020","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1002\/cpt.2526","article-title":"Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 genotype and clopidogrel therapy: 2022 update","volume":"112","author":"Lee","year":"2022","journal-title":"Clin. Pharmacol. Ther."},{"key":"B23","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.mjafi.2021.06.021","article-title":"Precision medicine: concept and tools","volume":"77","author":"Naithani","year":"2021","journal-title":"Med. J. Armed Forces India"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1016\/j.jacc.2018.02.029","article-title":"Pharmacogenomic approach to selecting antiplatelet therapy in patients with acute coronary syndromes: the PHARMCLO trial","volume":"71","author":"Notarangelo","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1016\/j.jcin.2014.04.020","article-title":"Impact of gene polymorphisms, platelet reactivity, and the SYNTAX score on 1-year clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention: the GEPRESS study","volume":"7","author":"Palmerini","year":"2014","journal-title":"JACC Cardiovasc Interv."},{"key":"B26","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1001\/jama.2020.12443","article-title":"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","volume":"324","author":"Pereira","year":"2020","journal-title":"Jama"},{"key":"B27","doi-asserted-by":"publisher","first-page":"e129","DOI":"10.1161\/CIR.0000000000001257","article-title":"CYP2C19 genetic testing for oral P2Y12 inhibitor therapy: a scientific statement from the American heart Association","volume":"150","author":"Pereira","year":"2024","journal-title":"Circulation"},{"key":"B28","doi-asserted-by":"publisher","first-page":"409","DOI":"10.2217\/fca.10.6","article-title":"Implementing genotype-guided antithrombotic therapy","volume":"6","author":"Seip","year":"2010","journal-title":"Future Cardiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1097\/FJC.0000000000000337","article-title":"Clinical value of CYP2C19 genetic testing for guiding the antiplatelet therapy in a Chinese population","volume":"67","author":"Shen","year":"2016","journal-title":"J. Cardiovasc Pharmacol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"S90","DOI":"10.1111\/epi.16539","article-title":"Precision medicine and therapies of the future","volume":"62","author":"Sisodiya","year":"2021","journal-title":"Epilepsia"},{"key":"B31","doi-asserted-by":"publisher","first-page":"730","DOI":"10.20452\/pamw.4087","article-title":"Can prasugrel decrease the extent of periprocedural myocardial injury during elective percutaneous coronary intervention?","volume":"127","author":"Tomaniak","year":"2017","journal-title":"Pol. Arch. Intern Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e0179349","DOI":"10.1371\/journal.pone.0179349","article-title":"Contemporary use of P2Y12-inhibitors in patients with acute coronary syndrome undergoing percutaneous coronary intervention in Austria: a prospective, multi-centre registry","volume":"12","author":"Tscharre","year":"2017","journal-title":"PLoS One"},{"key":"B33","doi-asserted-by":"publisher","first-page":"3736","DOI":"10.1016\/j.ijcard.2013.06.014","article-title":"Personalized antiplatelet therapy according to CYP2C19 genotype after percutaneous coronary intervention: a randomized control trial","volume":"168","author":"Xie","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41525-025-00479-3","article-title":"Discovery of ancestry-specific variants associated with clopidogrel response among Caribbean Hispanics","volume":"10","author":"Yang","year":"2025","journal-title":"NPJ Genom Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"839157","DOI":"10.3389\/fsurg.2022.839157","article-title":"Analysis of the guiding role of CYP2C19 gene combined with platelet function detection in antiplatelet therapy in patients with complex coronary artery disease after PCI","volume":"9","author":"Yu","year":"2022","journal-title":"Front. Surg."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1711350\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T16:10:26Z","timestamp":1774368626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1711350\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,24]]},"references-count":35,"alternative-id":["10.3389\/fphar.2026.1711350"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1711350","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,24]]},"article-number":"1711350"}}