{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T07:45:57Z","timestamp":1767167157496,"version":"build-2238731810"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose\u2014<\/jats:title>\n                    <jats:p>Recurrent ischemia risk is high in the acute period after cerebral ischemic events. Effects of antiplatelet agents may vary by time to loading dose (TLD). We explored the risk of recurrent events and safety and efficacy of ticagrelor versus aspirin in relation to TLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods\u2014<\/jats:title>\n                    <jats:p>We randomized 13\u2009199 patients with noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to 90-day ticagrelor or aspirin treatment within 24 hours of symptom onset. For this analysis, 13\u2009126 patients were categorized by TLD as &lt;12 hours or \u226512 hours from start of index event. The primary end point was the composite of stroke, myocardial infarction, or death within 90 days. Major bleeding was the primary safety end point.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results\u2014<\/jats:title>\n                    <jats:p>\n                      TLD was &lt;12 hours in 4403 (33.5%) and \u226512 hours in 8723 (66.5%). The Kaplan-Meier% for the primary end point for all patients with TLD&lt;12 hours was 7.5% versus 6.9% in TLD\u226512 hours. Among patients with TLD&lt;12 hours, the primary end point occurred in 147\/2196 (6.8%) randomized to ticagrelor and in 184\/2207 (8.3%) randomized to aspirin (hazard ratio, 0.79; 95% CI, 0.64\u20130.98;\n                      <jats:italic>P<\/jats:italic>\n                      =0.036). Among patients with TLD\u226512 hours, the primary end point occurred in 6.7% patients randomized to ticagrelor versus 7.0% to aspirin (hazard ratio, 0.95; 95% CI, 0.81\u20131.12;\n                      <jats:italic>P<\/jats:italic>\n                      =0.55). There was no significant treatment-by-TLD interaction. Major bleeding rates were comparable on ticagrelor and aspirin, regardless of TLD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>The event rate for the primary end point was higher in patients treated early (&lt;12 hours) versus later (\u226512 hours). In this exploratory analysis, a larger numerical difference in the primary end point was observed among patients on ticagrelor than on aspirin when TLD was &lt;12 hours compared with \u226512 hours, although the interaction terms for treatment-by-TLD were not significant. For major bleeding, no relation to TLD was observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration\u2014<\/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: NCT01994720.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.118.022675","type":"journal-article","created":{"date-parts":[[2019,2,19]],"date-time":"2019-02-19T05:01:07Z","timestamp":1550552467000},"page":"675-682","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Time to Loading Dose and Risk of Recurrent Events in the SOCRATES Trial"],"prefix":"10.1161","volume":"50","author":[{"given":"Carlos A.","family":"Molina","sequence":"first","affiliation":[{"name":"From the Stroke Unit, Hospital Vall d\u2019Hebron, Barcelona, Spain (C.A.M.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Claiborne","family":"Johnston","sequence":"additional","affiliation":[{"name":"Dean\u2019s Office, Dell Medical School, University of Texas, Austin (S.C.J.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per","family":"Ladenvall","sequence":"additional","affiliation":[{"name":"Global Medicines Development, AstraZeneca, Gothenburg, Sweden (P.L., H.D., P.H., M.K.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Amarenco","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Center, Bichat University Hospital and Paris-Diderot, Sorbonne University, France (P.A.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory W.","family":"Albers","sequence":"additional","affiliation":[{"name":"Stanford Stroke Center, Stanford University, Palo Alto, CA (G.W.A.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Denison","sequence":"additional","affiliation":[{"name":"Global Medicines Development, AstraZeneca, Gothenburg, Sweden (P.L., H.D., P.H., M.K.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Donald","family":"Easton","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, San Francisco (J.D.E.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott R.","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard University, Boston, MA (S.R.E.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Held","sequence":"additional","affiliation":[{"name":"Global Medicines Development, AstraZeneca, Gothenburg, Sweden (P.L., H.D., P.H., M.K.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikael","family":"Knutsson","sequence":"additional","affiliation":[{"name":"Global Medicines Development, AstraZeneca, Gothenburg, Sweden (P.L., H.D., P.H., M.K.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuo","family":"Minematsu","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan (K.M.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"R\u00f6ther","sequence":"additional","affiliation":[{"name":"Department of Neurology, Asklepios Klinik Altona, Hamburg, Germany (J.R.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tiantan Hospital, Beijing, China (Y.W.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.S. Lawrence","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Medicine &amp; Therapeutics, The Chinese University of Hong Kong (K.S.L.W.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the SOCRATES Steering Committee and Investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603060"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1215340"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70274-0"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.37991.635266.44"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30468-8"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)04011-7"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)04010-5"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.324.7329.71"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000158"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000131083"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.912550"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/ijs.12610"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000131658.80951.c3"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1614480"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2009.01.012"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.028566"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0258(20001015)19:19<2595::AID-SIM562>3.0.CO;2-M"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.017217"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.018132"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61448-2"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70248-X"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.654"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70060-0"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000163561.90680.1C"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70361\u20138"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0904327"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.03.100"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500857"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.020553"}],"updated-by":[{"DOI":"10.1161\/str.0000000000000186","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T00:00:00Z","timestamp":1553472000000}}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.118.022675","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:16:13Z","timestamp":1715598973000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.118.022675"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3]]},"references-count":29,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1161\/STROKEAHA.118.022675"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.118.022675","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3]]},"assertion":[{"value":"2018-08-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}