{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:20:59Z","timestamp":1790774459617,"version":"4.1.0"},"reference-count":19,"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":[[2022,6,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Peripheral artery disease (PAD) is associated with heightened risk for major adverse cardiovascular and limb events, but data on the burden of risk for total (first and potentially subsequent) events, and the association with polyvascular disease, are limited. This post hoc analysis of the EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) trial evaluated total cardiovascular and limb events among patients with symptomatic PAD, overall and by number of symptomatic vascular territories.<\/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                      In the EUCLID trial, patients with symptomatic PAD (lower extremity revascularization &gt;30\u00a0days before randomization or ankle\u2010brachial index \u22640.80) were randomized to treatment with ticagrelor or clopidogrel. Relative effects on total events (cardiovascular death; nonfatal myocardial infarction and ischemic stroke; acute limb ischemia, unstable angina, and transient ischemic attack requiring hospitalization; coronary, carotid, and peripheral revascularization procedures; and amputation for symptomatic PAD) were summarized by hazard ratios (HRs), whereas absolute risks were estimated by incidence rates and mean cumulative functions. Among 13\u00a0885 randomized patients, 7600 total cardiovascular and limb events occurred during a median 2.7\u00a0years of follow\u2010up, translating to 60.0 and 62.5 events per 100 patients through 3\u00a0years for the ticagrelor and clopidogrel groups, respectively (HR, 0.96; 95% CI, 0.89\u20131.03;\n                      <jats:italic>P<\/jats:italic>\n                      =0.27). Among 1393 patients with disease in 3 vascular territories, event accrual rates through 3\u00a0years for the ticagrelor and clopidogrel groups were 87.3 and 97.7 events per 100 patients, respectively. Absolute risk reductions for ticagrelor relative to clopidogrel at 3\u00a0years were \u22120.2, 6.7, and 10.3 events per 100 patients for 1, 2, and 3 affected vascular territories, respectively (\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>interaction<\/jats:sub>\n                      =0.09).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Patients with symptomatic PAD have nearly double the number of total events than first events, with rates reflecting the number of affected vascular territories. These findings highlight the clinical relevance of quantifying disease burden in terms of total events and the need for long\u2010term preventive treatments in high\u2010risk patient populations.<\/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:\/\/clinicaltrials.gov\/ct2\/show\/NCT01732822\">https:\/\/clinicaltrials.gov\/<\/jats:ext-link>\n                      ; Unique identifier: NCT01732822.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.122.025504","type":"journal-article","created":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T07:13:17Z","timestamp":1653635597000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Total Cardiovascular and Limb Events and the Impact of Polyvascular Disease in Chronic Symptomatic Peripheral Artery Disease"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0046-0264","authenticated-orcid":false,"given":"Michael","family":"Szarek","sequence":"first","affiliation":[{"name":"CPC Clinical Research Aurora CO"},{"name":"Department of Medicine University of Colorado Aurora CO"},{"name":"SUNY Downstate Health Sciences University Brooklyn NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie","family":"Hess","sequence":"additional","affiliation":[{"name":"CPC Clinical Research Aurora CO"},{"name":"Department of Medicine University of Colorado Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2393-0855","authenticated-orcid":false,"given":"Manesh R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Durham NC"},{"name":"Division of Cardiology Duke University Medical Center Durham NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7288-9596","authenticated-orcid":false,"given":"W. Schuyler","family":"Jones","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Durham NC"},{"name":"Division of Cardiology Duke University Medical Center Durham NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8216-4647","authenticated-orcid":false,"given":"Jeffrey S.","family":"Berger","sequence":"additional","affiliation":[{"name":"New York University School of Medicine New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Baumgartner","sequence":"additional","affiliation":[{"name":"Swiss Cardiovascular CenterInselspitalBern University HospitalUniversity of Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0682-7979","authenticated-orcid":false,"given":"Brian","family":"Katona","sequence":"additional","affiliation":[{"name":"AstraZeneca Gaithersburg Gaithersburg MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth W.","family":"Mahaffey","sequence":"additional","affiliation":[{"name":"Stanford Center for Clinical Research Stanford University School of Medicine Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2071-7132","authenticated-orcid":false,"given":"Lars","family":"Norgren","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health \u00d6rebro University \u00d6rebro Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juuso","family":"Blomster","sequence":"additional","affiliation":[{"name":"Turku University Hospital Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3732-4765","authenticated-orcid":false,"given":"Frank W.","family":"Rockhold","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Durham NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3413-7836","authenticated-orcid":false,"given":"Judith","family":"Hsia","sequence":"additional","affiliation":[{"name":"CPC Clinical Research Aurora CO"},{"name":"Department of Medicine University of Colorado Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Gerry R.","family":"Fowkes","sequence":"additional","affiliation":[{"name":"Usher Institute of Population Health Sciences and Informatics University of Edinburgh Edinburgh UK"}],"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":"CPC Clinical Research Aurora CO"},{"name":"Department of Medicine University of Colorado Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.297.11.1197"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.05.003"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.124248"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehn362"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611688"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2016.01.018"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2000052"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10985-019-09462-4"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.2307\/2530862"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1177\/1358863X18775594"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709118"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(18)30290-0"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.03.524"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.03.013"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.03.015"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.025880"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa649"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.08.035"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2009.09.025"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.122.025504","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T07:52:22Z","timestamp":1715586742000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.122.025504"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,7]]},"references-count":19,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,6,7]]}},"alternative-id":["10.1161\/JAHA.122.025504"],"URL":"https:\/\/doi.org\/10.1161\/jaha.122.025504","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,7]]},"assertion":[{"value":"2022-01-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e025504"}}