{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T08:46:19Z","timestamp":1769503579227,"version":"3.49.0"},"reference-count":31,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>The Clopidogrel With Aspirin in High-Risk Patients With Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial showed that ticagrelor-aspirin combination therapy reduced the risk of stroke compared with a clopidogrel-aspirin combination among carriers of CYP2C19<\/jats:italic> loss-of-function (LOF) alleles after a transient ischemic attack (TIA) or minor ischemic stroke. However, the association between the degree of CYP2C19<\/jats:italic> LOF and ideal treatment allocation remains unknown.<\/jats:p><\/jats:sec>Objective<\/jats:title>To investigate whether the efficacy and safety of ticagrelor-aspirin vs clopidogrel-aspirin are consistent with the expected degree of CYP2C19<\/jats:italic> LOF after TIA or minor stroke.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>CHANCE-2 was a multicenter, double-blind, double-dummy, placebo-controlled randomized clinical trial. Patients were enrolled at 202 centers in China from September 23, 2019, through March 22, 2021. Patients with at least two *2<\/jats:italic> or *3<\/jats:italic> alleles (*2\/*2<\/jats:italic>, *2\/*3<\/jats:italic>, or *3\/*3<\/jats:italic>) according to point-of-care genotyping were classified as \u201cpoor metabolizers,\u201d and those with one *2<\/jats:italic> or *3<\/jats:italic> allele (*1\/*2<\/jats:italic> or *1\/*3<\/jats:italic>) were classified as \u201cintermediate metabolizers.\u201d<\/jats:p><\/jats:sec>Interventions<\/jats:title>Patients were randomly assigned in a 1:1 ratio to receive ticagrelor (180-mg loading dose on day 1 followed by 90 mg twice daily for days 2-90) or clopidogrel (300-mg loading dose on day 1 followed by 75 mg\/d for days 2-90). All patients received aspirin (75- to 300-mg loading dose followed by 75 mg\/d for 21 days).<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary efficacy outcome was a new ischemic or hemorrhagic stroke. The secondary efficacy outcome was a composite of new clinical vascular events and individual ischemic stroke events within 3 months. The primary safety outcome was severe or moderate bleeding. Analyses were performed according to the intention-to-treat principle.<\/jats:p><\/jats:sec>Results<\/jats:title>Of the 6412 patients enrolled, the median age was 64.8 years (IQR, 57.0-71.4 years), and 4242 patients (66.2%) were men. Of the 6412 patients, 5001 (78.0%) were intermediate metabolizers, and 1411 (22.0%) were poor metabolizers. The primary outcome occurred less often with ticagrelor-aspirin vs clopidogrel-aspirin, irrespective of metabolizer status (6.0% [150 of 2486] vs 7.6% [191 of 2515]; hazard ratio [HR], 0.78 [95% CI, 0.63-0.97] among intermediate metabolizers and 5.7% [41 of 719] vs 7.5% [52 of 692]; HR, 0.77 [95% CI, 0.50-1.18] among poor metabolizers; P<\/jats:italic>\u2009=\u2009.88 for interaction). Patients taking ticagrelor-aspirin had a higher risk of any bleeding event compared with those taking clopidogrel-aspirin, irrespective of metabolizer status: 5.4% (134 of 2486) vs 2.6% (66 of 2512) (HR, 2.14 [95% CI, 1.59-2.89]) among intermediate metabolizers and 5.0% (36 of 719) vs 2.0% (14 of 692) (HR, 2.99 [95% CI, 1.51-5.93]) among poor metabolizers (P<\/jats:italic>\u2009=\u2009.66 for interaction).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>This prespecified analysis of a randomized clinical trial found no difference in treatment effect between poor and intermediate CYP2C19<\/jats:italic> metabolizers. The relative clinical efficacy and safety of ticagrelor-aspirin vs clopidogrel-aspirin were consistent across CYP2C19<\/jats:italic> genotypes.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT04078737<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.17037","type":"journal-article","created":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T17:19:16Z","timestamp":1686071956000},"page":"e2317037","source":"Crossref","is-referenced-by-count":9,"title":["Association of CYP2C19<\/i> Loss-of-Function Metabolizer Status With Stroke Risk Among Chinese Patients Treated With Ticagrelor-Aspirin vs Clopidogrel-Aspirin"],"prefix":"10.1001","volume":"6","author":[{"given":"Xuewei","family":"Xie","sequence":"first","affiliation":[{"name":"China National Clinical Research Center for Neurological Diseases, Beijing, China"},{"name":"Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Claiborne","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, San Francisco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anxin","family":"Wang","sequence":"additional","affiliation":[{"name":"China National Clinical Research Center for Neurological Diseases, Beijing, China"},{"name":"Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Xu","sequence":"additional","affiliation":[{"name":"China National Clinical Research Center for Neurological Diseases, Beijing, China"},{"name":"Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip M.","family":"Bath","sequence":"additional","affiliation":[{"name":"Stroke Trials Unit, Division of Clinical Neuroscience, University of 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Jiang","sequence":"additional","affiliation":[{"name":"China National Clinical Research Center for Neurological Diseases, Beijing, China"},{"name":"Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liping","family":"Liu","sequence":"additional","affiliation":[{"name":"China National Clinical Research Center for Neurological Diseases, Beijing, China"},{"name":"Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anding","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong Province, 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