{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:03:42Z","timestamp":1760295822901,"version":"3.41.2"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,10,26]]},"abstract":"\n Background<\/jats:title>\n The relationship between \u201con\u2010treatment\u201d low platelet reactivity and longitudinal risks of major bleeding dual antiplatelet therapy following acute coronary syndromes remains uncertain, especially for patients who do not undergo percutaneous coronary intervention.<\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We analyzed 2428 medically managed acute coronary syndromes patients from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes\n (TRILOGY ACS<\/jats:styled-content>\n ) trial who had serial platelet reactivity measurements (P2Y\n 12<\/jats:sub>\n reaction units;\n PRU<\/jats:styled-content>\n s) and were randomized to aspirin+prasugrel versus aspirin+clopidogrel for up to 30\u00a0months. Contal's method was used to determine whether a cut point for steady\u2010state\n PRU<\/jats:styled-content>\n values could distinguish high versus low bleeding risk using 2\u2010level composites: Global Use of Strategies to Open Occluded Coronary Arteries (\n GUSTO<\/jats:styled-content>\n ) severe\/life\u2010threatening or moderate bleeding unrelated to coronary artery bypass grafting (\n CABG<\/jats:styled-content>\n ) and non\u2010\n CABG<\/jats:styled-content>\n Thrombolysis In Myocardial Infarction (\n TIMI<\/jats:styled-content>\n ) major or minor bleeding. Exploratory analyses used 3\u2010level composites that incorporated mild and minimal\n GUSTO<\/jats:styled-content>\n and\n TIMI<\/jats:styled-content>\n events. Continuous measures of\n PRU<\/jats:styled-content>\n s (per 10\u2010unit decrease) were not independently associated with the 2\u2010level\n GUSTO<\/jats:styled-content>\n (adjusted hazard ratio [\n HR<\/jats:styled-content>\n ], 1.01; 95%\n CI<\/jats:styled-content>\n , 0.96\u20131.06) or\n TIMI<\/jats:styled-content>\n composites (1.02; 0.98\u20131.07). Furthermore, no\n PRU<\/jats:styled-content>\n cut point could significantly distinguish bleeding risk using the 2\u2010level composites. However, the\n PRU<\/jats:styled-content>\n cut point of 75 differentiated bleeding risk with the 3\u2010level composites of\n GUSTO<\/jats:styled-content>\n (26.5% vs 12.6%; adjusted\n HR<\/jats:styled-content>\n , 2.28; 95%\n CI<\/jats:styled-content>\n , 1.77\u20132.94;\n P<\/jats:italic>\n <0.001) and\n TIMI<\/jats:styled-content>\n bleeding events (25.9% vs 12.2%; adjusted\n HR<\/jats:styled-content>\n , 2.30; 95%\n CI<\/jats:styled-content>\n , 1.78\u20132.97;\n P<\/jats:italic>\n <0.001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Among medically managed non\u2010\n ST<\/jats:styled-content>\n \u2010segment elevation acute coronary syndromes patients receiving prolonged dual antiplatelet therapy,\n PRU<\/jats:styled-content>\n values were not significantly associated with the long\u2010term risk of major bleeding events, suggesting that low on\u2010treatment platelet reactivity does not independently predict serious bleeding risk.\n <\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration<\/jats:title>\n \n URL<\/jats:styled-content>\n :\n http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n . Unique identifier:\n NCT<\/jats:styled-content>\n 00699998.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.116.003977","type":"journal-article","created":{"date-parts":[[2016,11,5]],"date-time":"2016-11-05T02:19:14Z","timestamp":1478312354000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Relationship of Platelet Reactivity With Bleeding Outcomes During Long\u2010Term Treatment With Dual Antiplatelet Therapy for Medically Managed Patients With Non\u2010ST\u2010Segment Elevation Acute Coronary Syndromes"],"prefix":"10.1161","volume":"5","author":[{"given":"Jan H.","family":"Cornel","sequence":"first","affiliation":[{"name":"Medisch Centrum Alkmaar, Alkmaar, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. Magnus","family":"Ohman","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Durham, NC"},{"name":"Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Neely","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Durham, NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph A.","family":"Jakubowski","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Indianapolis, IN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harvey D.","family":"White","sequence":"additional","affiliation":[{"name":"Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Ardissino","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Azienda Ospedaliero\u2010Universitaria di Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith A.A.","family":"Fox","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, Scotland, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorairaj","family":"Prabhakaran","sequence":"additional","affiliation":[{"name":"Centre for Chronic Disease Control and Public Health Foundation of India, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul W.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Canadian VIGOUR Centre and Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Erlinge","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Udaya S.","family":"Tantry","sequence":"additional","affiliation":[{"name":"Sinai Center for Thrombosis Research, Baltimore, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul A.","family":"Gurbel","sequence":"additional","affiliation":[{"name":"Sinai Center for Thrombosis Research, Baltimore, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew T.","family":"Roe","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Durham, NC"},{"name":"Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv320"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.09.017"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa010746"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706482"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0904327"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe1502137"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03709.x"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2010.11.025"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.07.101"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1205512"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2010.04.022"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.17312"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-9473(98)00096-6"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs059"},{"key":"e_1_3_5_16_2","first-page":"45","article-title":"Enoxaparin vs unfractionated heparin in high\u2010risk patients with non\u2010ST\u2010segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial","volume":"292","author":"Ferguson JJ","year":"2004","unstructured":"Ferguson JJ, Califf RM, Antman EM, Cohen M, Grines CL, Goodman S, Kereiakes DJ, Langer A, Mahaffey KW, Nessel CC, Armstrong PW, Avezum A, Aylward P, Becker RC, Biasucci L, Borzak S, Col J, Frey MJ, Fry E, Gulba DC, Guneri S, Gurfinkel E, Harrington R, Hochman JS, Kleiman NS, Leon MB, Lopez\u2010Sendon JL, Pepine CJ, Ruzyllo W, Steinhubl SR, Teirstein PS, Toro\u2010Figueroa L, White H; SYNERGY Trial Investigators . Enoxaparin vs unfractionated heparin in high\u2010risk patients with non\u2010ST\u2010segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. JAMA. 2004;292:45\u201354.","journal-title":"JAMA"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr422"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0901316"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61451-8"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0195-668X(03)00485-8"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.828541"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.09.076"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2010.12.009"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.06.1323"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.002303"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.4244\/51"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv104"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209979"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61170-8"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCINTERVENTIONS.114.002106"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.116.003977","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T10:22:55Z","timestamp":1715595775000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.116.003977"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,26]]},"references-count":29,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2016,10,26]]}},"alternative-id":["10.1161\/JAHA.116.003977"],"URL":"https:\/\/doi.org\/10.1161\/jaha.116.003977","relation":{},"ISSN":["2047-9980"],"issn-type":[{"type":"electronic","value":"2047-9980"}],"subject":[],"published":{"date-parts":[[2016,10,26]]},"assertion":[{"value":"2016-05-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-09-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-11-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e003977"}}