{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T03:47:35Z","timestamp":1793850455375,"version":"4.6.1"},"reference-count":12,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,2,16]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Ticagrelor reduces ischemic risk but increases bleeding in patients with prior myocardial infarction. Identification of patients at lower bleeding risk is important in selecting patients who are likely to derive more favorable outcomes versus risk from this strategy.<\/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                      PEGASUS\u2010TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin\u2014Thrombolysis in Myocardial Infarction 54) randomized 21\u00a0162 patients with prior myocardial infarction in a 1:1:1 fashion to ticagrelor 60\u00a0mg or 90\u00a0mg twice daily or placebo, with ticagrelor 60\u00a0mg approved for long\u2010term use. TIMI major or minor bleeding was the primary end point for this analysis. Causes of bleeding were categorized by site and etiology, and independent predictors were identified. At 3 years, ticagrelor 60\u00a0mg increased the rate of TIMI major or minor bleeding by 2.0% versus placebo (1.4% placebo versus 3.4% ticagrelor). The bleeding excess was driven primarily by spontaneous gastrointestinal bleeds. A history of spontaneous bleeding requiring hospitalization and the presence of anemia were independent predictors of bleeding but not of ischemic risk. Patients with at least 1 risk predictor had 3\u2010fold higher rates of bleeding with ticagrelor 60 mg versus those who had neither (absolute risk increase, 4.4% versus 1.5%;\n                      <jats:italic>P<\/jats:italic>\n                      =0.01). Patients with neither predictor had a more favorable benefit profile with ticagrelor 60 mg versus placebo including lower mortality (hazard ratio, 0.79; 95% CI, 0.65\u20130.96;\n                      <jats:italic>P<\/jats:italic>\n                      interaction\u00a0=\u00a00.03).\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 myocardial infarction, bleeding with ticagrelor 60\u00a0mg twice daily is predominantly spontaneous gastrointestinal. A history of spontaneous bleeding requiring hospitalization or the presence of anemia identifies patients at higher risk of bleeding, and the absence of either identifies patients likely to have a more favorable net benefit with ticagrelor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p xml:lang=\"en\">\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: NCT01225562.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.120.017008","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T06:36:12Z","timestamp":1612852572000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["Predictors, Type, and Impact of Bleeding on the Net Clinical Benefit of Long\u2010Term Ticagrelor in Stable Patients With Prior Myocardial Infarction"],"prefix":"10.1161","volume":"10","author":[{"given":"Giulia","family":"Magnani","sequence":"first","affiliation":[{"name":"Parma University Hospital Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Ardissino","sequence":"additional","affiliation":[{"name":"Parma University Hospital Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KyungAh","family":"Im","sequence":"additional","affiliation":[{"name":"TIMI Study GroupBrigham and Women\u2019s Hospital Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6395-2098","authenticated-orcid":false,"given":"Andrzej","family":"Budaj","sequence":"additional","affiliation":[{"name":"Grochowski Hospital Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6677-6229","authenticated-orcid":false,"given":"Robert F.","family":"Storey","sequence":"additional","affiliation":[{"name":"University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6896-2941","authenticated-orcid":false,"given":"P. Gabriel","family":"Steg","sequence":"additional","affiliation":[{"name":"Dept de Cardiologie H\u00f4pital BichatH\u00f4pitaux de Paris Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1278-6245","authenticated-orcid":false,"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"TIMI Study GroupBrigham and Women\u2019s Hospital Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2793-1804","authenticated-orcid":false,"given":"Marc","family":"Cohen","sequence":"additional","affiliation":[{"name":"Newark Beth Israel Medical CenterRutgers Medical school Newark NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ton","family":"Oude Ophius","sequence":"additional","affiliation":[{"name":"Canisius Wilhelmina Ziekenhuis Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assen","family":"Goudev","sequence":"additional","affiliation":[{"name":"Queen Giovanna University Hospital St Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Parkhomenko","sequence":"additional","affiliation":[{"name":"Institute of Cardiology Kiev Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Kamensky","sequence":"additional","affiliation":[{"name":"University Hospital Bratislava Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8451-2131","authenticated-orcid":false,"given":"Dominick J.","family":"Angiolillo","sequence":"additional","affiliation":[{"name":"University of FloridaCollege of Medicine Jacksonville FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"L\u00f3pez\u2010Send\u00f3n","sequence":"additional","affiliation":[{"name":"Hosp Univrio La Paz Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Johanson","sequence":"additional","affiliation":[{"name":"AstraZeneca M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3472-626X","authenticated-orcid":false,"given":"Eugene","family":"Braunwald","sequence":"additional","affiliation":[{"name":"TIMI Study GroupBrigham and Women\u2019s Hospital Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0691-3359","authenticated-orcid":false,"given":"Marc S.","family":"Sabatine","sequence":"additional","affiliation":[{"name":"TIMI Study GroupBrigham and Women\u2019s Hospital Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9860-3584","authenticated-orcid":false,"given":"Marc P.","family":"Bonaca","sequence":"additional","affiliation":[{"name":"University of ColoradoSchool of Medicine Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500857"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/ehjcvp\/pvz020"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.06.1323"},{"issue":"437","key":"e_1_3_1_5_2","first-page":"e5","article-title":"Design and rationale for the prevention of cardiovascular events in patients with prior heart attack using ticagrelor compared to placebo on a background of aspirin\u2010thrombolysis in myocardial infarction 54 (PEGASUS\u2010TIMI 54) trial","volume":"167","author":"Bonaca MP","year":"2014","unstructured":"Bonaca MP, Bhatt DL, Braunwald E, Cohen M, Steg PG, Storey RF, Held P, Jensen EC, Sabatine MS. Design and rationale for the prevention of cardiovascular events in patients with prior heart attack using ticagrelor compared to placebo on a background of aspirin\u2010thrombolysis in myocardial infarction 54 (PEGASUS\u2010TIMI 54) trial. 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Eur Heart J. 2016;37:400\u2013408.","journal-title":"Eur Heart J"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30397-5"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2016.1017"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.120.017008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T07:01:41Z","timestamp":1715583701000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.120.017008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,16]]},"references-count":12,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,2,16]]}},"alternative-id":["10.1161\/JAHA.120.017008"],"URL":"https:\/\/doi.org\/10.1161\/jaha.120.017008","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,16]]},"assertion":[{"value":"2020-04-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e017008"}}