{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T16:49:57Z","timestamp":1788194997388,"version":"build-2803163510"},"reference-count":13,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2015,3,10]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Vorapaxar is a protease\u2010activated receptor\u20101 antagonist approved by the U.S. Food and Drug Administration (FDA) for the reduction of thrombotic cardiovascular (CV) events in patients with a history of myocardial infarction (MI) and peripheral artery disease (PAD), without a previous stroke or transient ischemic attack (TIA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      We examined the efficacy and safety of vorapaxar in the intended use population, considering 20\u00a0170 patients randomized in the multinational, double\u2010blinded, placebo\u2010controlled TRA 2\u00b0P\u2010TIMI 50 trial. Of these, 16\u00a0897 qualified with a history of MI in the prior 2\u00a0weeks to 1\u00a0year and 3273 with PAD. At baseline 97% of the patients were treated with aspirin, 71% with a thienopyridine, and 93% a statin. At 3\u00a0years, the endpoint of CV death, MI, or stroke was significantly reduced with vorapaxar compared with placebo (7.9% versus 9.5%, HR, 0.80; 95% CI 0.73 to 0.89;\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001). Vorapaxar also significantly reduced the composite of CV death, MI, stroke, and urgent coronary revascularization (10.1% versus 11.8%, HR, 0.83; 95% CI 0.76 to 0.90;\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001), as well as the rate of CV death or MI (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001). The safety endpoint of GUSTO moderate or severe bleeding, was increased in the vorapaxar group (3.7 versus 2.4, HR, 1.55; 95% CI 1.30 to 1.86,\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001). Intracranial bleeding (ICH) was 0.6% versus 0.4%,\n                      <jats:italic>P<\/jats:italic>\n                      =0.10 with vorapaxar versus placebo, with fatal bleeding 0.2% versus 0.2%;\n                      <jats:italic>P<\/jats:italic>\n                      =0.70.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">In patients with prior MI or PAD who have not had a previous stroke or TIA, vorapaxar added to standard therapy is effective for long\u2010term secondary prevention of thrombotic CV events, while increasing moderate or severe bleeding.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p xml:lang=\"en\">URL: clinicaltrials.gov Unique Identifier: NCT00526474.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.114.001505","type":"journal-article","created":{"date-parts":[[2015,3,20]],"date-time":"2015-03-20T10:17:29Z","timestamp":1426846649000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":66,"title":["Efficacy and Safety of Vorapaxar as Approved for Clinical Use in the United States"],"prefix":"10.1161","volume":"4","author":[{"given":"Giulia","family":"Magnani","sequence":"first","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc P.","family":"Bonaca","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Braunwald","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Dalby","sequence":"additional","affiliation":[{"name":"Milpark Hospital, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith A. A.","family":"Fox","sequence":"additional","affiliation":[{"name":"Cardiovascular Research, University of Edinburgh, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina A.","family":"Murphy","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Carlos","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Heart Institute (InCor)\u2014University of S\u00e3o Paulo Medical School, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ton","family":"Oude Ophuis","sequence":"additional","affiliation":[{"name":"Canisius\u2014Wilhelmina Hospital, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin M.","family":"Scirica","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jindrich","family":"Spinar","sequence":"additional","affiliation":[{"name":"University Hospital Brno, Masaryk University, Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Theroux","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute and University of Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Morrow","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.2217\/fca.09.27"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1200933"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61269-0"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.000679"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.111.000433"},{"issue":"335","key":"e_1_3_3_7_2","first-page":"e3","article-title":"Evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease: design and rationale for the Thrombin\u2010Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2\u00b0P)\u2010TIMI 50 trial","volume":"158","author":"Morrow DA","year":"2009","unstructured":"Morrow DA, Scirica BM, Fox KA, Berman G, Strony J, Veltri E, Bonaca MP, Fish P, McCabe CH, Braunwald E; TRA 2P\u2013TIMI 50 Investigators . Evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease: design and rationale for the Thrombin\u2010Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2\u00b0P)\u2010TIMI 50 trial. Am Heart J. 2009;158:335\u2013341:e3.","journal-title":"Am Heart J"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr236"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706482"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0904327"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16721-4"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1204133"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0805002"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1109719"}],"updated-by":[{"DOI":"10.1161\/jaha.115.000633","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2015,4,27]],"date-time":"2015-04-27T00:00:00Z","timestamp":1430092800000}}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.114.001505","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T06:24:16Z","timestamp":1715581456000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.114.001505"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,10]]},"references-count":13,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,3,10]]}},"alternative-id":["10.1161\/JAHA.114.001505"],"URL":"https:\/\/doi.org\/10.1161\/jaha.114.001505","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,10]]},"assertion":[{"value":"2014-10-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-03-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e001505"}}