{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T01:56:23Z","timestamp":1781661383226,"version":"3.54.5"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is recommended for secondary prevention in patients with a minor stroke or transient ischemic attack. However, the effectiveness of DAPT can be significantly influenced by genetic variations. This study aimed to estimate the impact of multiple single-nucleotide polymorphisms across various genes on DAPT efficacy using polygenic risk score (PRS).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>In this post hoc analysis, we included 2905 patients from the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events), which enrolled a total of 5170 patients in China between October 2009 and July 2012. The primary outcome was new stroke within 90 days. Sixteen single-nucleotide polymorphisms across 7 genes involved in clopidogrel metabolism were selected for PRS development. PRS were calculated by summing single-nucleotide polymorphisms from each individual. The Cox proportional-hazards regression model was utilized to estimate the hazard ratio (HR) and 95% CIs of PRS. The predictive value of PRS was estimated by C statistic and compared with a previously validated model.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              The elevated PRSs were associated with an increased risk of new stroke within 90 days (\n              <jats:italic>P<\/jats:italic>\n              <jats:sub>trend<\/jats:sub>\n              =0.01). The efficacy of DAPT versus aspirin alone in preventing 1-year composite vascular events was significantly different between patients with low (adjusted HR, 0.47 [95% CI, 0.31\u20130.71]) and high PRSs (adjusted HR, 0.84 [95% CI, 0.60\u20131.18];\n              <jats:italic>P<\/jats:italic>\n              <jats:sub>interaction<\/jats:sub>\n              =0.03). In patients receiving DAPT, higher PRSs were associated with increased risk of new stroke and composite vascular events at 90 days (adjusted HR per SD increase was 1.51 [95% CI, 1.15\u20131.99]) and at 1 year (adjusted HR per SD increase was 1.34 [95% CI, 1.08\u20131.67]). The C statistic for predicting 90-day new stroke using the PRS developed in this study was 0.57 (95% CI, 0.52\u20130.62), compared with 0.52 (95% CI, 0.48\u20130.55) for the ABCD-GENE score.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Using PRS integrating multiple genes may enhance the precision of secondary prevention strategies for patients with minor stroke or transient ischemic attack in the short and long term.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>REGISTRATION:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT00979589.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.124.049140","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T10:02:38Z","timestamp":1741341758000},"page":"818-827","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Polygenic Risk Score for the Efficacy of Clopidogrel in Patients With Minor Stroke or Transient Ischemic Attack: A Post Hoc Analysis of the CHANCE Trial"],"prefix":"10.1161","volume":"56","clinical-trial-number":[{"clinical-trial-number":"nct00979589","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Xin","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital (X.Q., H.-Q.G., Yong Jiang, X.H., X.M., Y.W., Z.L.), Capital Medical University, Beijing, China."},{"name":"China National Clinical Research Center for Neurological Diseases, Beijing, China (X.Q., Yingyu Jiang, H.-Q.G., Yong Jiang, X.H., X.M., Y.W., Z.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingyu","family":"Jiang","sequence":"additional","affiliation":[{"name":"China National Clinical Research Center for Neurological Diseases, Beijing, China (X.Q., Yingyu Jiang, H.-Q.G., Yong Jiang, X.H., X.M., Y.W., Z.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1608-1856","authenticated-orcid":true,"given":"Hong-Qiu","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital (X.Q., H.-Q.G., Yong Jiang, X.H., X.M., Y.W., Z.L.), Capital Medical University, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7700-6054","authenticated-orcid":true,"given":"Yong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital (X.Q., H.-Q.G., Yong Jiang, X.H., X.M., Y.W., Z.L.), Capital Medical University, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9948-6869","authenticated-orcid":true,"given":"Xinying","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital (X.Q., H.-Q.G., Yong Jiang, X.H., X.M., Y.W., Z.L.), Capital Medical University, Beijing, China."},{"name":"School of Population Medicine and Public Health, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing, China (X.H.)."},{"name":"China National Clinical Research Center for Neurological Diseases, Beijing, China (X.Q., Yingyu Jiang, H.-Q.G., Yong Jiang, X.H., X.M., Y.W., Z.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8764-9739","authenticated-orcid":true,"given":"Xia","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital (X.Q., H.-Q.G., Yong Jiang, X.H., X.M., Y.W., Z.L.), Capital Medical University, Beijing, China."},{"name":"China National Clinical Research Center for Neurological Diseases, Beijing, China (X.Q., Yingyu Jiang, H.-Q.G., Yong Jiang, X.H., X.M., Y.W., Z.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9976-2341","authenticated-orcid":true,"given":"Yongjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital (X.Q., H.-Q.G., Yong Jiang, X.H., X.M., Y.W., Z.L.), Capital Medical University, Beijing, China."},{"name":"Clinical Center for Precision Medicine in Stroke (Y.W.), Capital Medical University, Beijing, China."},{"name":"China National Clinical Research Center for Neurological Diseases, Beijing, China (X.Q., Yingyu Jiang, H.-Q.G., Yong Jiang, X.H., X.M., Y.W., Z.L.)."},{"name":"Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, China (Y.W., Z.L.)."},{"name":"Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China (Y.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4713-5418","authenticated-orcid":true,"given":"Zixiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital (X.Q., H.-Q.G., Yong Jiang, X.H., X.M., Y.W., Z.L.), Capital Medical University, Beijing, China."},{"name":"China National Clinical Research Center for Neurological Diseases, Beijing, China (X.Q., Yingyu Jiang, H.-Q.G., Yong Jiang, X.H., X.M., Y.W., Z.L.)."},{"name":"Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, China (Y.W., 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