{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T10:13:05Z","timestamp":1789726385600,"version":"4.0.1"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"25","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2018,12,18]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The glucagon-like peptide-1 analog liraglutide reduced cardiovascular events and mortality in patients with type 2 diabetes mellitus in the LEADER trial (Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes). In a post hoc analysis, we evaluated the efficacy of liraglutide in those with and without a history of myocardial infarction (MI) and\/or stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>LEADER was a randomized trial of liraglutide (1.8 mg or maximum tolerated dose) versus placebo in 9340 patients with type 2 diabetes mellitus and high cardiovascular risk, with a median follow-up of 3.8 years. The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke (major adverse cardiovascular events). Risk groups in this post hoc analysis were defined by history of MI\/stroke, established atherosclerotic cardiovascular disease without MI\/stroke, or cardiovascular risk factors alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Of the 9340 patients, 3692 (39.5%) had a history of MI\/stroke, 3083 (33.0%) had established atherosclerotic cardiovascular disease without MI\/stroke, and 2565 (27.5%) had risk factors alone. Major adverse cardiovascular events occurred in 18.8% of patients with a history of MI\/stroke (incidence rate, 5.0 per 100 patient-years), 11.6% of patients with established atherosclerotic cardiovascular disease without MI\/stroke (incidence rate, 3.0 per 100 patient-years), and 9.8% of patients with cardiovascular risk factors alone (incidence rate, 2.6 per 100 patient-years). Liraglutide reduced major adverse cardiovascular events in patients with a history of MI\/stroke (322 of 1865 [17.3%] versus 372 of 1827 patients [20.4%]; hazard ratio, 0.85; 95% CI, 0.73\u20130.99) and in those with established atherosclerotic cardiovascular disease without MI\/stroke (158 of 1538 [10.3%] versus 199 of 1545 patients [12.9%]; hazard ratio, 0.76; 95% CI, 0.62\u20130.94) compared with placebo. In patients with risk factors alone, the hazard ratio for liraglutide versus placebo was 1.08 (95% CI, 0.84\u20131.38,\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>interaction<\/jats:sub>\n                      =0.11). Similar results were seen for secondary outcomes across risk groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>In this post hoc analysis of patients with type 2 diabetes mellitus and high cardiovascular risk, liraglutide reduced cardiovascular outcomes both in patients with a history of MI\/stroke and in those with established atherosclerotic cardiovascular disease without MI\/stroke. The cardiovascular effect appeared neutral in patients with cardiovascular risk factors alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration:<\/jats:title>\n                    <jats:p>\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: NCT01179048.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.118.034516","type":"journal-article","created":{"date-parts":[[2018,12,17]],"date-time":"2018-12-17T14:02:41Z","timestamp":1545055361000},"page":"2884-2894","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":120,"title":["Effects of Liraglutide on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus With or Without History of Myocardial Infarction or Stroke"],"prefix":"10.1161","volume":"138","author":[{"given":"Subodh","family":"Verma","sequence":"first","affiliation":[{"name":"Division of Cardiac Surgery (S.V.), Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil R.","family":"Poulter","sequence":"additional","affiliation":[{"name":"Imperial College London, United Kingdom (N.R.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA (D.L.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"Bain","sequence":"additional","affiliation":[{"name":"Institute of Life Science, Swansea University, United Kingdom (S.C.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B.","family":"Buse","sequence":"additional","affiliation":[{"name":"University of North Carolina School of Medicine, Chapel Hill (J.B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence A.","family":"Leiter","sequence":"additional","affiliation":[{"name":"St Michael\u2019s Hospital and University of Toronto (L.A.L.), Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Nauck","sequence":"additional","affiliation":[{"name":"Diabetes Center Bochum-Hattingen, St Josef-Hospital, Ruhr-University Bochum, Germany (M.A.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Pratley","sequence":"additional","affiliation":[{"name":"Florida Hospital Translational Research Institute for Metabolism and Diabetes, Orlando (R.E.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Zinman","sequence":"additional","affiliation":[{"name":"Lunenfeld Tanebaum Research Institute, Mount Sinai Hospital, University of Toronto, Canada (B.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D.","family":"\u00d8rsted","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark (D.D.\u00d8., T.M.F., S.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tea","family":"Monk Fries","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark (D.D.\u00d8., T.M.F., S.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark (D.D.\u00d8., T.M.F., S.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven P.","family":"Marso","sequence":"additional","affiliation":[{"name":"Hospital Corporation of America (HCA) Midwest Health Heart &amp; Vascular Institute, Kansas City, MO (S.P.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"For the LEADER Publication Committee on Behalf of the LEADER Trial Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.014796"},{"key":"e_1_3_4_3_2","unstructured":"Centers for Disease Control and Prevention. National diabetes statistics report. 2014. https:\/\/www.cdc.gov\/diabetes\/pdfs\/data\/2014-report-estimates-of-diabetes-and-its-burden-in-the-united-states.pdf. 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