{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:40:35Z","timestamp":1783125635614,"version":"3.54.6"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p><jats:italic>CYP2C19<\/jats:italic> loss\u2010of\u2010function (LOF) alleles decrease the antiplatelet effect of clopidogrel following percutaneous coronary intervention (PCI) in patients presenting with acute coronary syndrome (ACS). The impact of genotype in patients undergoing PCI for stable ischemic heart disease (SIHD) in real\u2010world populations is less clear. We determined time to major adverse cardiac event (MACE), defined as the composite of cardiovascular death, stroke, or myocardial infarction, within 12\u2009months following PCI in the VA Million Veteran Program (MVP) participants treated with clopidogrel from 1\/1\/2009 to 9\/30\/2017. Among 9061 Veterans (mean age 66.4\u2009\u00b1\u20098.7\u2009years, 98% male, 13% Black); 43% had ACS, 57% had SIHD, and 28% carried a <jats:italic>CYP2C19<\/jats:italic> LOF allele. In total, 619 patients (6.8%) experienced MACE, 317 (8.2%) in the ACS group and 302 (5.8%) in the SIHD group. Overall, a trend toward increased MACE risk was seen in the LOF carriers vs. non\u2010carriers (adjusted hazard ratio [aHR] 1.13, confidence interval [95% CI] 0.98\u20131.31, <jats:italic>P<\/jats:italic>\u2009=\u20090.097), with a stronger risk among those presenting with ACS (aHR 1.20, 95% CI 0.98\u20131.47; <jats:italic>P<\/jats:italic>\u2009=\u20090.083). In post hoc analyses, LOF was associated with a significantly increased risk of MACE among younger (&lt;\u200966\u2009years) patients with ACS (aHR 1.41 [1.04\u20131.91], <jats:italic>P<\/jats:italic>\u2009=\u20090.028); however, no difference in risk was observed among older patients (aHR 1.07, 95% CI 0.80\u20131.40, <jats:italic>P<\/jats:italic>\u2009=\u20090.676). There was no impact of genotype in patients with SIHD (aHR 1.09, 95% CI 0.82\u20131.44, <jats:italic>P<\/jats:italic>\u2009=\u20090.565). Clinical factors may be more important than <jats:italic>CYP2C19<\/jats:italic> genotype in determining the risk of MACE in older Veterans treated with clopidogrel undergoing PCI for ACS.<\/jats:p>","DOI":"10.1002\/cpt.3741","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T10:44:24Z","timestamp":1748947464000},"page":"876-884","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<i>CYP2C19<\/i> Polymorphisms and Clinical Outcomes Following Percutaneous Coronary Intervention in the Million Veteran Program"],"prefix":"10.1002","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4663-8953","authenticated-orcid":false,"given":"Catherine","family":"Chanfreau\u2010Coffinier","sequence":"first","affiliation":[{"name":"VA Salt Lake City Heath Care System  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5179-5075","authenticated-orcid":false,"given":"Kevin A.","family":"Friede","sequence":"additional","affiliation":[{"name":"Division of Cardiology University of North Carolina School of Medicine  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Plomondon","sequence":"additional","affiliation":[{"name":"CART Program, Office of Quality and Patient Safety Veterans Health Administration  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Min","family":"Lee","sequence":"additional","affiliation":[{"name":"VA Salt Lake City Heath Care System  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Lu","sequence":"additional","affiliation":[{"name":"VA Salt Lake City Heath Care System  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tia","family":"Dinatale","sequence":"additional","affiliation":[{"name":"VA Salt Lake City Heath Care System  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4898-3865","authenticated-orcid":false,"given":"Scott L.","family":"DuVall","sequence":"additional","affiliation":[{"name":"VA Salt Lake City Heath Care System  Salt Lake City Utah USA"},{"name":"Division of Epidemiology University of Utah School of Medicine  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6113-5564","authenticated-orcid":false,"given":"Jason L.","family":"Vassy","sequence":"additional","affiliation":[{"name":"VA Boston Healthcare System, Harvard Medical School, and Brigham and Women's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen W.","family":"Waldo","sequence":"additional","affiliation":[{"name":"CART Program, Office of Quality and Patient Safety Veterans Health Administration  Washington DC USA"},{"name":"Rocky Mountain Regional VA Medical Center University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Cleator","sequence":"additional","affiliation":[{"name":"Centennial Heart at Skyline Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Maddox","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine in St. Louis  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Rader","sequence":"additional","affiliation":[{"name":"University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2349-0009","authenticated-orcid":false,"given":"Themistocles L.","family":"Assimes","sequence":"additional","affiliation":[{"name":"VA Palo Alto Healthcare System Stanford University  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Damrauer","sequence":"additional","affiliation":[{"name":"University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Corporal Michael J. 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