{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:10:37Z","timestamp":1790975437741,"version":"4.1.0"},"reference-count":17,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2011,5,3]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Atopaxar (E5555) is a reversible protease-activated receptor-1 thrombin receptor antagonist that interferes with platelet signaling. The primary objective of the Lessons From Antagonizing the Cellular Effects of Thrombin\u2013Acute Coronary Syndromes (LANCELOT\u2014ACS) trial was to evaluate the safety and tolerability of atopaxar in patients with ACS.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Six hundred and three subjects were randomized within 72 hours of non\u2013ST-elevation ACS to 1 of 3 doses of atopaxar (400-mg loading dose followed by 50, 100, or 200 mg daily) or matching placebo. The incidence of Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) major or minor bleeding did not differ significantly between the combined atopaxar and placebo groups (3.08% versus 2.17%, respectively;\n              <jats:italic>P<\/jats:italic>\n              =0.63), and there was no dose-related trend (\n              <jats:italic>P<\/jats:italic>\n              =0.80). The incidence of CURE major bleeding was numerically higher in the atopaxar group compared with the placebo group (1.8% versus 0%;\n              <jats:italic>P<\/jats:italic>\n              =0.12). The incidence of cardiovascular death, myocardial infarction, stroke, or recurrent ischemia was similar between the atopaxar and placebo arms (8.03% versus 7.75%;\n              <jats:italic>P<\/jats:italic>\n              =0.93). The incidence of CV death, MI, or stroke was 5.63% in the placebo group and 3.25% in the combined atopaxar group (\n              <jats:italic>P<\/jats:italic>\n              =0.20). Dose-dependent trends for efficacy were not seen. Atopaxar significantly reduced ischemia on continuous ECG monitoring (Holter) at 48 hours compared with placebo (relative risk, 0.67;\n              <jats:italic>P<\/jats:italic>\n              =0.02). Transient dose-dependent transaminase elevation and relative QTc prolongation were observed with the highest doses of atopaxar.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion\u2014<\/jats:title>\n            <jats:p>In patients after ACS, atopaxar significantly reduced early ischemia on Holter monitoring without a significant increase in major or minor bleeding. Larger trials are required to fully establish the efficacy and safety of atopaxar.<\/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=\"http:\/\/www.ClinicalTrials.gov\">http:\/\/www.ClinicalTrials.gov<\/jats:ext-link>\n              . Unique identifier: NCT00548587.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.110.000786","type":"journal-article","created":{"date-parts":[[2011,4,19]],"date-time":"2011-04-19T04:20:00Z","timestamp":1303186800000},"page":"1843-1853","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":139,"title":["Safety and Tolerability of Atopaxar in the Treatment of Patients With Acute Coronary Syndromes"],"prefix":"10.1161","volume":"123","author":[{"given":"Michelle L.","family":"O'Donoghue","sequence":"first","affiliation":[{"name":"From the TIMI Study Group, Brigham and Women's Hospital (M.L.O., S.D.W., C.F.C.); VA Boston Healthcare System and TIMI Study Group, Brigham and Women's Hospital (D.L.B.), Boston, MA; Canadian Heart Research Centre and Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario (S.G.G.); UCD Conway Institute, University College, Dublin, Ireland (D.J.F.); University of Florida College of Medicine, Jacksonville (D.J.A.); Division of Cardiology, Tokai University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Brigham and Women's Hospital (M.L.O., S.D.W., C.F.C.); VA Boston Healthcare System and TIMI Study Group, Brigham and Women's Hospital (D.L.B.), Boston, MA; Canadian Heart Research Centre and Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario (S.G.G.); UCD Conway Institute, University College, Dublin, Ireland (D.J.F.); University of Florida College of Medicine, Jacksonville (D.J.A.); Division of Cardiology, Tokai University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.","family":"Wiviott","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Brigham and Women's Hospital (M.L.O., S.D.W., C.F.C.); VA Boston Healthcare System and TIMI Study Group, Brigham and Women's Hospital (D.L.B.), Boston, MA; Canadian Heart Research Centre and Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario (S.G.G.); UCD Conway Institute, University College, Dublin, Ireland (D.J.F.); University of Florida College of Medicine, Jacksonville (D.J.A.); Division of Cardiology, Tokai University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun G.","family":"Goodman","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Brigham and Women's Hospital (M.L.O., S.D.W., C.F.C.); VA Boston Healthcare System and TIMI Study Group, Brigham and Women's Hospital (D.L.B.), Boston, MA; Canadian Heart Research Centre and Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario (S.G.G.); UCD Conway Institute, University College, Dublin, Ireland (D.J.F.); University of Florida College of Medicine, Jacksonville (D.J.A.); Division of Cardiology, Tokai University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desmond J.","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Brigham and Women's Hospital (M.L.O., S.D.W., C.F.C.); VA Boston Healthcare System and TIMI Study Group, Brigham and Women's Hospital (D.L.B.), Boston, MA; Canadian Heart Research Centre and Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario (S.G.G.); UCD Conway Institute, University College, Dublin, Ireland (D.J.F.); University of Florida College of Medicine, Jacksonville (D.J.A.); Division of Cardiology, Tokai University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominick J.","family":"Angiolillo","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Brigham and Women's Hospital (M.L.O., S.D.W., C.F.C.); VA Boston Healthcare System and TIMI Study Group, Brigham and Women's Hospital (D.L.B.), Boston, MA; Canadian Heart Research Centre and Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario (S.G.G.); UCD Conway Institute, University College, Dublin, Ireland (D.J.F.); University of Florida College of Medicine, Jacksonville (D.J.A.); Division of Cardiology, Tokai University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Goto","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Brigham and Women's Hospital (M.L.O., S.D.W., C.F.C.); VA Boston Healthcare System and TIMI Study Group, Brigham and Women's Hospital (D.L.B.), Boston, MA; Canadian Heart Research Centre and Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario (S.G.G.); UCD Conway Institute, University College, Dublin, Ireland (D.J.F.); University of Florida College of Medicine, Jacksonville (D.J.A.); Division of Cardiology, Tokai University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Montalescot","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Brigham and Women's Hospital (M.L.O., S.D.W., C.F.C.); VA Boston Healthcare System and TIMI Study Group, Brigham and Women's Hospital (D.L.B.), Boston, MA; Canadian Heart Research Centre and Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario (S.G.G.); UCD Conway Institute, University College, Dublin, Ireland (D.J.F.); University of Florida College of Medicine, Jacksonville (D.J.A.); Division of Cardiology, Tokai University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Zeymer","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Brigham and Women's Hospital (M.L.O., S.D.W., C.F.C.); VA Boston Healthcare System and TIMI Study Group, Brigham and Women's Hospital (D.L.B.), Boston, MA; Canadian Heart Research Centre and Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario (S.G.G.); UCD Conway Institute, University College, Dublin, Ireland (D.J.F.); University of Florida College of Medicine, Jacksonville (D.J.A.); Division of Cardiology, Tokai University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip E.","family":"Aylward","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Brigham and Women's Hospital (M.L.O., S.D.W., C.F.C.); VA Boston Healthcare System and TIMI Study Group, Brigham and Women's Hospital (D.L.B.), Boston, MA; Canadian Heart Research Centre and Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario (S.G.G.); UCD Conway Institute, University College, Dublin, Ireland (D.J.F.); University of Florida College of Medicine, Jacksonville (D.J.A.); Division of Cardiology, Tokai University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Guetta","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Brigham and Women's Hospital (M.L.O., S.D.W., C.F.C.); VA Boston Healthcare System and TIMI Study Group, Brigham and Women's Hospital (D.L.B.), Boston, MA; Canadian Heart Research Centre and Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario (S.G.G.); UCD Conway Institute, University College, Dublin, Ireland (D.J.F.); University of Florida College of Medicine, Jacksonville (D.J.A.); Division of Cardiology, Tokai University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariusz","family":"Dudek","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Brigham and Women's Hospital (M.L.O., S.D.W., C.F.C.); VA Boston Healthcare System and TIMI Study Group, Brigham and Women's Hospital (D.L.B.), Boston, MA; Canadian Heart Research Centre and Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario (S.G.G.); UCD Conway Institute, University College, Dublin, Ireland (D.J.F.); University of Florida College of Medicine, Jacksonville (D.J.A.); Division of Cardiology, Tokai University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafal","family":"Ziecina","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Brigham and Women's Hospital (M.L.O., S.D.W., C.F.C.); VA Boston Healthcare System and TIMI Study Group, Brigham and Women's Hospital (D.L.B.), Boston, MA; Canadian Heart Research Centre and Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario (S.G.G.); UCD Conway Institute, University College, Dublin, Ireland (D.J.F.); University of Florida College of Medicine, Jacksonville (D.J.A.); Division of Cardiology, Tokai University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles F.","family":"Contant","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Brigham and Women's Hospital (M.L.O., S.D.W., C.F.C.); VA Boston Healthcare System and TIMI Study Group, Brigham and Women's Hospital (D.L.B.), Boston, MA; Canadian Heart Research Centre and Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario (S.G.G.); UCD Conway Institute, University College, Dublin, Ireland (D.J.F.); University of Florida College of Medicine, Jacksonville (D.J.A.); Division of Cardiology, Tokai University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus D.","family":"Flather","sequence":"additional","affiliation":[{"name":"From the TIMI Study Group, Brigham and Women's Hospital (M.L.O., S.D.W., C.F.C.); VA Boston Healthcare System and TIMI Study Group, Brigham and Women's Hospital (D.L.B.), Boston, MA; Canadian Heart Research Centre and Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario (S.G.G.); UCD Conway Institute, University College, Dublin, Ireland (D.J.F.); University of Florida College of Medicine, Jacksonville (D.J.A.); Division of Cardiology, Tokai University School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra071014"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.107.181940"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehm161"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa010746"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60503-1"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000072771.11429.83"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.105.574830"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehp504"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000091201.39590.cb"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.76.1.142"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH08-12-0805"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm0603670"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60230-0"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2009.06.027"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2009.07.001"},{"key":"e_1_3_5_17_2","unstructured":"Merck. Merck says additional information provided to investigators in clinical study of vorapaxar [press release]. January 19 2011. http:\/\/www.merck.com\/newsroom\/news-release-archive\/research-and-development\/2011_0119.html. Accessed March 30 2011."},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq320"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.110.000786","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T05:36:10Z","timestamp":1715578570000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.110.000786"}},"subtitle":["The Lessons From Antagonizing the Cellular Effects of Thrombin\u2013Acute Coronary Syndromes Trial"],"short-title":[],"issued":{"date-parts":[[2011,5,3]]},"references-count":17,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2011,5,3]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.110.000786"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.110.000786","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,5,3]]},"assertion":[{"value":"2010-10-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-01-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-04-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}