{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:03:14Z","timestamp":1792623794342,"version":"4.5.0"},"reference-count":14,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose:<\/jats:title>\n            <jats:p>\n              Clopidogrel is an antiplatelet drug that is metabolized to its active form by the CYP2C19 enzyme. The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) found a significant interaction between loss-of-function allele status for the\n              <jats:italic>CYP2C19<\/jats:italic>\n              gene and the effect of dual antiplatelet therapy with aspirin and clopidogrel on the rate of early recurrent stroke following acute transient ischemic attack\/minor stroke. The POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial), similar in design to CHANCE but performed largely in North America and Europe, demonstrated a reduction in early recurrent stroke with dual antiplatelet therapy compared with aspirin alone. This substudy was done to evaluate a potential interaction between loss-of-function\n              <jats:italic>CYP2C19<\/jats:italic>\n              alleles and outcome by treatment group in POINT.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              Of the 269 sites in 10 countries that enrolled patients in POINT, 134 sites participated in this substudy. DNA samples were genotyped for\n              <jats:italic>CYP2C19<\/jats:italic>\n              *2, *3, and *17 alleles and classified as being carriers or noncarriers of loss-of-function alleles. Major ischemia consisted of ischemic stroke, myocardial infarction, or ischemic vascular death.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Nine hundred thirty-two patients provided analyzable DNA. The rates of major ischemia were 6.7% for the aspirin group versus 2.3% for the dual antiplatelet therapy group (hazard ratio, 0.33 [95% CI, 0.09\u20131.21];\n              <jats:italic>P<\/jats:italic>\n              =0.09) among carriers of loss-of-function allele. The rates of major ischemia were 5.6% for the aspirin group versus 3.7% for the dual antiplatelet therapy group (hazard ratio, 0.65 [95% CI, 0.32\u20131.34];\n              <jats:italic>P<\/jats:italic>\n              =0.25) among noncarriers. There was no significant interaction by genotype for major ischemia (\n              <jats:italic>P<\/jats:italic>\n              =0.36) or stroke (\n              <jats:italic>P<\/jats:italic>\n              =0.33).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              This substudy of POINT found no significant interaction with\n              <jats:italic>CYP2C19<\/jats:italic>\n              loss-of-function carrier status and outcome by treatment group. Failure to confirm the findings from the CHANCE trial may be because the loss-of-function alleles tested are not clinically important in this context or because the 2 trials had differences in racial\/ethnic composition. Additionally, differences between the 2 trials might be due to chance as our statistical power was limited to 50%.\n            <\/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: NCT00991029.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.119.028713","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T13:27:37Z","timestamp":1592400457000},"page":"2058-2065","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["Efficacy of Clopidogrel for Prevention of Stroke Based on\n            <i>CYP2C19<\/i>\n            Allele Status in the POINT Trial"],"prefix":"10.1161","volume":"51","clinical-trial-number":[{"clinical-trial-number":"nct00991029","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4475-8142","authenticated-orcid":false,"given":"James F.","family":"Meschia","sequence":"first","affiliation":[{"name":"Departments of Neurology (J.F.M.), Mayo Clinic, Jacksonville, FL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald L.","family":"Walton","sequence":"additional","affiliation":[{"name":"Neuroscience (R.L.W., L.P.F., O.A.R.), Mayo Clinic, Jacksonville, FL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca P.","family":"Farrugia","sequence":"additional","affiliation":[{"name":"Neuroscience (R.L.W., L.P.F., O.A.R.), Mayo Clinic, Jacksonville, FL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen A.","family":"Ross","sequence":"additional","affiliation":[{"name":"Neuroscience (R.L.W., L.P.F., O.A.R.), Mayo Clinic, Jacksonville, FL."},{"name":"Clinical Genomics (O.A.R.), Mayo Clinic, Jacksonville, FL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan J.","family":"Elm","sequence":"additional","affiliation":[{"name":"Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston (J.J.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Farrant","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, San Francisco (M.F., J.D.E., A.S.K., K.G.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Meurer","sequence":"additional","affiliation":[{"name":"Departments of Emergency Medicine (W.J.M., W.B.), University of Michigan, Ann Arbor."},{"name":"Neurology (W.J.M., W.B.), University of Michigan, Ann Arbor."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne S.","family":"Lindblad","sequence":"additional","affiliation":[{"name":"The Emmes Corporation, Rockville, MD (A.S.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Barsan","sequence":"additional","affiliation":[{"name":"Departments of Emergency Medicine (W.J.M., W.B.), University of Michigan, Ann Arbor."},{"name":"Neurology (W.J.M., W.B.), University of Michigan, Ann Arbor."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilou","family":"Ching","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Buffalo Jacobs School of Medicine and Biomedical Sciences, NY (M.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Temple University, Philadelphia, PA (N.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine and Neurology, Emory University, Atlanta, GA (M.R., F.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadi","family":"Nahab","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine and Neurology, Emory University, Atlanta, GA (M.R., F.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Donald","family":"Easton","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, San Francisco (M.F., J.D.E., A.S.K., K.G.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony S.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, San Francisco (M.F., J.D.E., A.S.K., K.G.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla G.","family":"Zurita","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, San Francisco (M.F., J.D.E., A.S.K., K.G.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett","family":"Cucchiara","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pennsylvania, Philadelphia (B.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Claiborne","family":"Johnston","sequence":"additional","affiliation":[{"name":"Dean\u2019s Office, Dell Medical School, Dell Medical Center, Austin, TX (S.C.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.1232"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0809171"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61845-0"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808227"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1215340"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.8662"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1800410"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.25.11.2220"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60150-0"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.5930"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.03.037"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2012.04.020"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.01.030"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.769"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.119.028713","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T14:49:03Z","timestamp":1715611743000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.119.028713"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7]]},"references-count":14,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1161\/STROKEAHA.119.028713"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.119.028713","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7]]},"assertion":[{"value":"2019-12-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}