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However, patients receiving standard antiplatelet prophylaxis still face a substantial risk of recurrent events. Strategies involving 3 antithrombotic agents with different modes of action have now been tested. In Thrombin Receptor Antagonists for Clinical Event Reduction (<jats:styled-content style=\"fixed-case\">TRA\u2010CER<\/jats:styled-content>), compared with standard care alone, bleeding complications including intracranial hemorrhage (<jats:styled-content style=\"fixed-case\">ICH<\/jats:styled-content>) were increased with the addition of vorapaxar, without efficacy benefit. In Trial to Assess the Effects of <jats:styled-content style=\"fixed-case\">SCH<\/jats:styled-content> 530348 in Preventing Heart Attack and Stroke in Patients With Atherosclerosis (<jats:styled-content style=\"fixed-case\">TRA<\/jats:styled-content> 2\u00b0P\u2013<jats:styled-content style=\"fixed-case\">TIMI<\/jats:styled-content> 50), the addition of vorapaxar reduced recurrent events compared with standard care in stable patients with prior myocardial infarction. This study was terminated early in patients with prior stroke owing to excess <jats:styled-content style=\"fixed-case\">ICH<\/jats:styled-content>, though an increased risk of <jats:styled-content style=\"fixed-case\">ICH<\/jats:styled-content> or fatal bleeding was not detected in patients with prior myocardial infarction. The Apixaban for Prevention of Acute Ischemic and Safety Events 2 (<jats:styled-content style=\"fixed-case\">APPRAISE<\/jats:styled-content>\u20102) trial of standard\u2010dose apixaban added to standard care in patients with <jats:styled-content style=\"fixed-case\">ACS<\/jats:styled-content> was also stopped early owing to excess serious bleeding. However, in Rivaroxaban in Combination With Aspirin Alone or With Aspirin and a Thienopyridine in Patients With Acute Coronary Syndromes (<jats:styled-content style=\"fixed-case\">ATLAS ACS<\/jats:styled-content> 2 <jats:styled-content style=\"fixed-case\">TIMI<\/jats:styled-content> 51), fatal bleeding or fatal <jats:styled-content style=\"fixed-case\">ICH<\/jats:styled-content> did not increase with low\u2010dose rivaroxaban added to low\u2010dose acetylsalicylic acid\u2010based standard care compared with standard care alone. In that trial, a significant reduction of recurrent vascular events was shown with 3 antithrombotic regimens compared with standard care. Therefore, depending on drug dose and patient population, further reductions in recurrent vascular events after <jats:styled-content style=\"fixed-case\">ACS<\/jats:styled-content> may be possible in future clinical practice, with a favorable benefit\u2010risk profile.<\/jats:p>","DOI":"10.1002\/clc.22233","type":"journal-article","created":{"date-parts":[[2014,1,22]],"date-time":"2014-01-22T17:55:54Z","timestamp":1390413354000},"page":"178-187","source":"Crossref","is-referenced-by-count":17,"title":["New Antithrombotics for Secondary Prevention of Acute Coronary Syndrome"],"prefix":"10.1002","volume":"37","author":[{"given":"Shinya","family":"Goto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiko","family":"Tomita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,1,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2010.199"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra000650"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1112570"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.93.7.1354"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0904327"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706482"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa010746"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112277"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06797"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1538-7836.2003.00349.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-08-0465"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)86616-4"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-4431.2009.00383.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehp504"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111110"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108941"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.72.8.3073"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08-0672"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.72.6.1177"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61088-4"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000091201.39590.CB"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr236"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.10.015"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs215"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0b013e31820f2f3e"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.4.1406"},{"key":"e_1_2_9_28_1","doi-asserted-by":"crossref","unstructured":"Antiplatelet Trialists' Collaboration. 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