{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:11:34Z","timestamp":1788315094773,"version":"build-2803163510"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Clopidogrel is a widely used antiplatelet agent used to prevent adverse events for patients suffering from acute coronary syndromes and ischemic stroke. As a prodrug, clopidogrel must be converted to the active form through the enzyme cytochrome (CYP) P450 2C19 (among other enzymes). Individuals carrying a loss of function (LOF) allele (i.e., *2 and\/or *3) have reduced pharmacologic efficacy. Ticagrelor is an alternative antiplatelet medication that is not a prodrug.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We reviewed the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE2) Trial demonstrating the inferiority of clopidogrel dual therapy with aspirin vs ticagrelor dual therapy to prevent adverse events among patients suffering from a mild stroke among Chinese patients who carried a CYP2C19 LOF. We also summarized the pharmacogenomic testing policies within Chinese clinical laboratories after publication of this trial, and tabulated the CYP2C19 LOF allele frequencies among ancestries, as a criteria for justifying the expense required for establishing pharmacogenomic testing services for other populations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The CHANCE2 trial showed that stroke patients carrying a CYP2C19 LOF allele(s) had a reduction of 1.6% for recurrent stroke for those treated with ticagrelor vs clopidogrel. The LOF allele frequency was highest among Pacific Island and Western and Central Asian (e.g., Han Chinese) patients and lowest among European, Latin, and Hispanic Latino patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Pharmacogenomic testing for CYP2C19 variants is more economically justified for laboratories that serve a population enriched with CYP2C19 LOF alleles, than populations exhibiting a lower allele frequency. Within a clinical laboratory offering testing, restricting testing to certain populations is not ethical.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jalm\/jfaf041","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T17:33:11Z","timestamp":1744824791000},"page":"976-982","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacogenomic Testing for <i>CYP2C19<\/i> Variants among Stroke Patients Treated with Clopidogrel: Opportunity for the Clinical Laboratory?"],"prefix":"10.1093","volume":"10","author":[{"given":"Alan H B","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, University of California , San Francisco, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody M","family":"Orahoske","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of California , San Francisco, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanmin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Chicago , Chicago, IL ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Estabil","sequence":"additional","affiliation":[{"name":"Cipherome, Inc. , San Jose, CA ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiang-Teck J","family":"Yeo","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Chicago , Chicago, IL ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"2025070109064668600_jfaf041-B1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2217\/pme.09.1","article-title":"Implementation of pharmacogenomics into the clinical practice of therapeutics: issues for the clinician and the laboratorian","volume":"6","author":"Wu","year":"2009","journal-title":"Person Med"},{"key":"2025070109064668600_jfaf041-B2","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1002\/cpt.2039","article-title":"Impact of the CYP2C19*17 allele on outcomes in patients receiving genotype-guided antiplatelet therapy after percutaneous coronary intervention","volume":"109","author":"Lee","year":"2021","journal-title":"Clin Pharmacol Ther"},{"key":"2025070109064668600_jfaf041-B3","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1161\/CIR.0b013e3181ee08ed","article-title":"ACCF\/AHA clopidogrel clinical alert: approaches to the FDA \u201cboxed warning\u201d. A report of the American College of Cardiology Foundation Task Forse on Clinical Expert Consensus Documents and the American Heart Association","volume":"122","author":"Holmes","year":"2010","journal-title":"Circulation"},{"key":"2025070109064668600_jfaf041-B4","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1016\/S0140-6736(21)00533-X","article-title":"Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis","volume":"397","author":"Galli","year":"2021","journal-title":"Lancet"},{"key":"2025070109064668600_jfaf041-B5","first-page":"e129","article-title":"CYP2C19 genetic testing for oral P2Y12 inhibitor therapy: a scientific statement from the American Heart Association","volume":"150","author":"Pereira","year":"2014","journal-title":"Circulation"},{"key":"2025070109064668600_jfaf041-B6","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1007\/s40262-015-0290-2","article-title":"Ticagrelor: pharmacokinetic, pharmacodynamic, and pharmacogenetic profile: an update","volume":"54","author":"Teng","year":"2015","journal-title":"Clin Pharmacokinet"},{"key":"2025070109064668600_jfaf041-B7","first-page":"420","article-title":"Association of ticagrelor vs clopidogrel with major adverse coronary events in patients with acute coronary syndrome undergoing percutaneous coronary intervention","volume":"180","author":"Turgeon","year":"2020","journal-title":"JAMA"},{"key":"2025070109064668600_jfaf041-B8","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1097\/FPC.0b013e3283385420","article-title":"Clopidogrel pathway","volume":"20","author":"Sangkuhl","year":"2010","journal-title":"Phamacogen Genom"},{"key":"2025070109064668600_jfaf041-B9","author":"National Institute for Health and Care Excellences"},{"key":"2025070109064668600_jfaf041-B10","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa1215340","article-title":"Clopidogrel with aspirin in acute minor stroke or transient ischemic attack","volume":"369","author":"Wang","year":"2013","journal-title":"N Engl J Med"},{"key":"2025070109064668600_jfaf041-B11","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1056\/NEJMoa2111749","article-title":"Ticagrelor versus clopidogrel in CYP2C19 loss-of-function carriers with stroke or TIA","volume":"385","author":"Wang","year":"2021","journal-title":"N Engl J Med"},{"key":"2025070109064668600_jfaf041-B12","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1002\/cpt.2350","article-title":"An evidence-based framework for evaluating pharmacogenomics knowledge for personalized medicine","volume":"110","author":"Whirl-Carrillo","year":"2021","journal-title":"Clin Pharmacol Ther"},{"key":"2025070109064668600_jfaf041-B13","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/clpt.2012.96","article-title":"Pharmacogenomics knowledge for personalized medicine","volume":"92","author":"Whirl-Carrillo","year":"2012","journal-title":"Clin Pharmacol Ther"},{"key":"2025070109064668600_jfaf041-B14","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1093\/ehjcvp\/pvac037","article-title":"Cost-effectiveness of clopidogrel vs. ticagrelor in patients of 70 years or order with non-ST-elevation acute coronary syndrome","volume":"9","author":"Van den Broek","year":"2022","journal-title":"Eur Hear J Cardiovasc Pharmacother"}],"container-title":["The Journal of Applied Laboratory Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jalm\/article-pdf\/10\/4\/976\/62940877\/jfaf041.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jalm\/article-pdf\/10\/4\/976\/62940877\/jfaf041.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T13:06:58Z","timestamp":1751375218000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jalm\/article\/10\/4\/976\/8114711"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,16]]},"references-count":14,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4,16]]},"published-print":{"date-parts":[[2025,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jalm\/jfaf041","relation":{},"ISSN":["2475-7241"],"issn-type":[{"value":"2475-7241","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,7]]},"published":{"date-parts":[[2025,4,16]]}}}