{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:50:07Z","timestamp":1791528607976,"version":"4.3.4"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100015339","name":"ACCP Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Recurrent stroke accounts for substantial morbidity and mortality worldwide, with up to 25% of ischemic strokes occurring in patients with prior strokes. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is standard for secondary prevention after minor acute ischemic stroke (AIS) or high\u2010risk transient ischemic attack (TIA). However, clopidogrel efficacy is reduced in carriers of cytochrome P450 2C19 (\n CYP2C19<\/jats:italic>\n ) loss\u2010of\u2010function (LOF) alleles. Although genotype\u2010guided DAPT has been shown to improve outcomes, the limited availability, high cost, and turnaround time of\n CYP2C19<\/jats:italic>\n genotyping constrain real\u2010world use. P2Y12 reaction units (PRUs) measured by the VerifyNow P2Y12 assay represent a potentially accessible alternative, but their relevance in the cerebrovascular population remains unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To investigate the viability of PRUs as a surrogate biomarker for clopidogrel resistance, we aimed to assess the association of PRUs with\n CYP2C19<\/jats:italic>\n genotype, which has been previously proven as predictive of clinical outcomes in patients receiving DAPT after AIS.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We conducted a prospective observational study of adults with non\u2010cardioembolic minor AIS or high\u2010risk TIA treated with 21\u2009days of DAPT between December 2021 and May 2023. PRUs were measured \u2265\u200912\u2009h after a clopidogrel loading dose. The primary outcome was the group difference in PRUs by\n CYP2C19<\/jats:italic>\n LOF carrier status. Secondary outcomes included associations between high platelet reactivity (PRU \u2265\u2009208),\n CYP2C19<\/jats:italic>\n genotype, and 30\u2010day stroke recurrence.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of the 35 patients included in the primary analysis, 17% were\n CYP2C19<\/jats:italic>\n LOF carriers. Mean PRUs were significantly higher in LOF carriers (265 vs. 161;\n p<\/jats:italic>\n \u2009<\u20090.01), and high platelet reactivity was more frequent among carriers (83% vs. 21%;\n p<\/jats:italic>\n \u2009<\u20090.01) compared with noncarriers, respectively. Twenty\u2010seven patients completed 30\u2010day follow\u2010up; 26% reported recurrent stroke symptoms, but neither\n CYP2C19<\/jats:italic>\n LOF status nor high platelet reactivity was associated. Post hoc application of the ABCD\u2010GENE score did not improve prediction of high platelet reactivity or clinical outcomes.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n PRUs appear to vary by\n CYP2C19<\/jats:italic>\n genotype in patients receiving DAPT after minor AIS or TIA, suggesting utility as a surrogate marker of clopidogrel nonresponse when genotyping is unavailable. However, PRUs were not associated with short\u2010term clinical outcomes.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/phar.70201","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T07:51:22Z","timestamp":1789113082000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association Between\n \n CYP2C19<\/i>\n <\/scp>\n Genotype and\n P2Y12<\/scp>\n Reaction Units in Patients Receiving Clopidogrel After Acute Ischemic Stroke: A Prospective, Observational Study"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7751-4948","authenticated-orcid":false,"given":"Rachael M.","family":"Stone","sequence":"first","affiliation":[{"name":"Department of Neurology University of Virginia School of Medicine Charlottesville Virginia USA"},{"name":"Department of Pharmacy University of Virginia Health Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Virginia Health Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonya","family":"Gunter","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia School of Medicine Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew T.","family":"Weko","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia School of Medicine Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carter","family":"Gottschalk","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia School of Medicine Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheyenne","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia School of Medicine Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Ramsey","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia School of Medicine Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miah Perch","family":"Weatherspoon","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia School of Medicine Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradford B.","family":"Worrall","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia School of Medicine Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001303"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538\u20107836.2006.02249.x"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002888"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1215340"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1800410"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000375"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2526"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.8662"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2111749"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10557\u2010024\u201007627\u20104"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.70402"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/ane.13655"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcin.2022.09.007"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(16)31323\u2010X"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.5551\/jat.63369"},{"key":"e_1_2_12_17_1","unstructured":"pBrainMD VerifyNow Reference Guide. 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