{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:07:14Z","timestamp":1792141634165,"version":"4.4.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2017,1,3]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>\n              The association of genetic polymorphisms and clopidogrel efficacy in patients with ischemic stroke or transient ischemic attack (TIA) remains controversial. We performed a systematic review and meta-analysis to assess the association between genetic polymorphisms, especially\n              <jats:italic>CYP2C19<\/jats:italic>\n              genotype, and clopidogrel efficacy for ischemic stroke or TIA.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>We conducted a comprehensive search of PubMed and EMBASE from their inceptions to June 24, 2016. Studies that reported clopidogrel-treated patients with stroke or TIA and with information on genetic polymorphisms were included. The end points were stroke, composite vascular events, and any bleeding.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Among 15 studies of 4762 patients with stroke or TIA treated with clopidogrel, carriers of\n              <jats:italic>CYP2C19<\/jats:italic>\n              loss-of-function alleles (*2, *3, and *8) were at increased risk of stroke in comparison with noncarriers (12.0% versus 5.8%; risk ratio, 1.92, 95% confidence interval, 1.57\u20132.35;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). Composite vascular events were also more frequent in carriers of\n              <jats:italic>CYP2C19<\/jats:italic>\n              loss-of-function alleles than in noncarriers (13.7% versus 9.4%; risk ratio, 1.51, 95% confidence interval, 1.10\u20132.06;\n              <jats:italic>P<\/jats:italic>\n              =0.01), whereas bleeding rates were similar (2.4% versus 3.1%; risk ratio, 0.89, 95% confidence interval, 0.58\u20131.35;\n              <jats:italic>P<\/jats:italic>\n              =0.59). There was no evidence of statistical heterogeneity among the included studies for stroke, but there was for composite vascular events. Genetic variants other than\n              <jats:italic>CYP2C19<\/jats:italic>\n              were not associated with clinical outcomes, with the exception that significant associations of\n              <jats:italic>PON1<\/jats:italic>\n              ,\n              <jats:italic>P2Y12<\/jats:italic>\n              , and\n              <jats:italic>COX-1<\/jats:italic>\n              with outcomes were observed in 1 study.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              Carriers of\n              <jats:italic>CYP2C19<\/jats:italic>\n              loss-of-function alleles are at greater risk of stroke and composite vascular events than noncarriers among patients with ischemic stroke or TIA treated with clopidogrel.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.116.024913","type":"journal-article","created":{"date-parts":[[2016,11,3]],"date-time":"2016-11-03T02:14:04Z","timestamp":1478139244000},"page":"21-33","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":266,"title":["Genetic Polymorphisms and Clopidogrel Efficacy for Acute Ischemic Stroke or Transient Ischemic Attack"],"prefix":"10.1161","volume":"135","author":[{"given":"Yuesong","family":"Pan","sequence":"first","affiliation":[{"name":"From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqi","family":"Chen","sequence":"additional","affiliation":[{"name":"From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Xu","sequence":"additional","affiliation":[{"name":"From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyang","family":"Yi","sequence":"additional","affiliation":[{"name":"From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Han","sequence":"additional","affiliation":[{"name":"From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingwu","family":"Yang","sequence":"additional","affiliation":[{"name":"From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2019an","family":"Huang","sequence":"additional","affiliation":[{"name":"From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Claiborne","family":"Johnston","sequence":"additional","affiliation":[{"name":"From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingquan","family":"Zhao","sequence":"additional","affiliation":[{"name":"From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Liu","sequence":"additional","affiliation":[{"name":"From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyao","family":"Wang","sequence":"additional","affiliation":[{"name":"From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Wang","sequence":"additional","affiliation":[{"name":"From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilong","family":"Wang","sequence":"additional","affiliation":[{"name":"From Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); China National Clinical Research Center for Neurological Diseases, Beijing (Y.P., W.C., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Center of Stroke, Beijing Institute for Brain Disorders, China (Y.P., W.C., L.H., X.Z., L.L., Q.Z., G.W., Yongjun Wang, Yilong Wang); Beijing Key Laboratory of Translational Medicine for Cerebrovascular..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)09457-3"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1215340"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1586\/ern.10.203"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12111"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.12.071"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2011.227652"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808227"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12173"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.000823"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.11.037"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.114.001652"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.8662"},{"key":"e_1_3_3_14_2","unstructured":"Wells GA Shea B O\u2019Connell D Peterson J Welch V Losos M Tugwell P. 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