{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:41:46Z","timestamp":1788932506099,"version":"build-2803163510"},"reference-count":23,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Clopidogrel is used as secondary prevention after cerebral ischaemia. Previous, mainly Asian, studies have shown that genetic variations in <jats:italic>CYP2C19<\/jats:italic> are associated with an increased risk of recurrent stroke in clopidogrel\u2010treated patients. Evidence on the impact of this drug\u2013gene interaction in European neurology patients is currently limited. The aim of this study is to compare the prevalence of <jats:italic>CYP2C19<\/jats:italic> loss\u2010of\u2010function (LoF) alleles in a population with recurrent cerebral ischaemia to two reference groups from the same region.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>CYP2C19<\/jats:italic>\u2010genotyping (*2 and *3) was performed in clopidogrel\u2010treated patients who presented with a recurrent ischaemic stroke\/transient ischaemic attack (TIA). Genotype distributions were compared with two reference groups; a cohort of consecutive patients who underwent elective coronary stent implantation and a cohort of healthy Dutch volunteers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 188 cases with a recurrent ischaemic event were identified, of whom 38 (20.2%) experienced an early recurrent event (24\u2009hours to 90\u2009days after the previous event). Among the total case group, 43.6% of the patients carried at least one <jats:italic>CYP2C19<\/jats:italic> LoF allele, compared with 27.6% and 24.7% in respectively the cardiology and the healthy volunteers reference groups (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001 for both comparisons). Among the cases with an early recurrent event, 55.3% of patients were carriers of at least one <jats:italic>CYP2C19<\/jats:italic> LoF allele (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this clopidogrel\u2010treated population with recurrent cerebral ischaemia, the frequency of <jats:italic>CYP2C19<\/jats:italic> LoF alleles was significantly higher than in reference groups, especially in early recurrent events. This study adds to the growing body of evidence that genotype\u2010guided antiplatelet therapy could improve patient outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15282","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T23:04:52Z","timestamp":1645139092000},"page":"3335-3340","source":"Crossref","is-referenced-by-count":10,"title":["Increased frequency of <i>CYP2C19<\/i> loss\u2010of\u2010function alleles in clopidogrel\u2010treated patients with recurrent cerebral ischemia"],"prefix":"10.1111","volume":"88","author":[{"given":"Crista","family":"Minderhoud","sequence":"first","affiliation":[{"name":"University Medical Center Utrecht  Utrecht Netherlands"},{"name":"St. Antonius Hospital  Nieuwegein Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila S.","family":"Otten","sequence":"additional","affiliation":[{"name":"St. Antonius Hospital  Nieuwegein Netherlands"},{"name":"Radboud University Medical Center  Nijmegen Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter H. E.","family":"Hilkens","sequence":"additional","affiliation":[{"name":"St. Antonius Hospital  Nieuwegein Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel P. H.","family":"van den Broek","sequence":"additional","affiliation":[{"name":"St. Antonius Hospital  Nieuwegein Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3134-6608","authenticated-orcid":false,"given":"Ankie M.","family":"Harmsze","sequence":"additional","affiliation":[{"name":"St. Antonius Hospital  Nieuwegein Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1215340"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1586\/ern.10.203"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.11.044"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0809171"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2011.227652"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.024913"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.105"},{"key":"e_1_2_11_9_1","unstructured":"Regionale kerncijfers provincie Utrecht.Centraal Bureau voor Statistiek.https:\/\/opendata.cbs.nl\/statline\/#\/CBS\/nl\/dataset\/70072NED\/table?fromstatweb. 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