{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T05:42:06Z","timestamp":1785822126852,"version":"3.56.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Quality and Outcomes"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The ENGAGE AF\u2013TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation\u2013Thrombolysis in Myocardial Infarction 48) demonstrated noninferiority of once-daily 60 mg (30 mg dose-reduced) edoxaban compared with warfarin for prevention of stroke\/systemic embolism in patients with atrial fibrillation. No previous analysis has explored the impact of treatment with edoxaban versus warfarin on rates of hospitalizations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec sec-type=\"methods\">\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Detailed healthcare resource utilization data from ENGAGE AF\u2013TIMI 48 for the 14\u2009024 randomized patients who received at least one dose of study drug were used to compare the rates of bleeding- and cardiovascular-related hospitalizations for edoxaban versus warfarin. Hospitalization rates were calculated for each treatment group, and relative rates were estimated using Poisson regression. The influence of patient characteristics on the impact of edoxaban versus warfarin was evaluated through the inclusion of interaction terms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec sec-type=\"results\">\n            <jats:title>Results<\/jats:title>\n            <jats:p>\n              The overall rate of cardiovascular- or bleeding-related hospitalization was significantly lower for edoxaban than warfarin (relative rate [RR], 0.91 [95% CI, 0.85\u20130.97],\n              <jats:italic>P<\/jats:italic>\n              =0.003). Rates of hospitalizations for cardiovascular reasons (RR, 0.91 [95% CI, 0.85\u20130.97],\n              <jats:italic>P<\/jats:italic>\n              =0.004), stroke (RR, 0.80 [95% CI, 0.72\u20130.88],\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001), and for each stroke subtype (ischemic: RR, 0.89 [95% CI, 0.81\u20130.99],\n              <jats:italic>P<\/jats:italic>\n              =0.03; hemorrhagic: RR, 0.60 [95% CI, 0.54\u20130.68],\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001) were also lower for edoxaban. Notably, significantly greater reductions with edoxaban versus warfarin were seen for ischemic stroke\u2013related hospitalizations in vitamin K antagonist naive patients and patients with CHADS\n              <jats:sub>2<\/jats:sub>\n              scores 4 to 6, previous stroke or transient ischemic attack, age \u226575, and no previous coronary artery disease. For nonstroke bleeding\u2013related hospitalizations, greater reductions with edoxaban were seen in vitamin K antagonist naive patients, patients with CHADS\n              <jats:sub>2<\/jats:sub>\n              scores 4 to 6, and patients with moderate renal dysfunction.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Edoxaban 60 mg (30 mg dose-reduced) was associated with a significantly lower overall rate of cardiovascular- or bleeding-related hospitalization and significant reductions in the subcategories of cardiovascular-related, stroke-related, bleed-related, and nonstroke cardiovascular\u2013related hospitalizations, when compared with warfarin. These results suggest the potential for cost offsets with edoxaban, with even greater reductions in higher-risk patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>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: NCT00781391\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circoutcomes.120.006511","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T10:00:14Z","timestamp":1604570414000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Cardiovascular- and Bleeding-Related Hospitalization Rates With Edoxaban Versus Warfarin in Patients With Atrial Fibrillation Based on Results of the ENGAGE AF\u2013TIMI 48 Trial"],"prefix":"10.1161","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct00781391","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Katherine","family":"Vilain","sequence":"first","affiliation":[{"name":"Saint Luke\u2019s Mid America Heart Institute, Kansas City, MO (K.V., H.L., E.A.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Li","sequence":"additional","affiliation":[{"name":"Saint Luke\u2019s Mid America Heart Institute, Kansas City, MO (K.V., H.L., E.A.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wingham J.","family":"Kwong","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo, Inc, Basking Ridge, NJ (W.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliott M.","family":"Antman","sequence":"additional","affiliation":[{"name":"Saint Luke\u2019s Mid America Heart Institute, Kansas City, MO (K.V., H.L., E.A.M.)."},{"name":"TIMI Study Group, Brigham and Women\u2019s Hospital, Boston, MA (E.M.A., C.T.R., E.B., R.P.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian T.","family":"Ruff","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Brigham and Women\u2019s Hospital, Boston, MA (E.M.A., C.T.R., E.B., R.P.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3472-626X","authenticated-orcid":true,"given":"Eugene","family":"Braunwald","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Brigham and Women\u2019s Hospital, Boston, MA (E.M.A., C.T.R., E.B., R.P.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9163-724X","authenticated-orcid":true,"given":"David J.","family":"Cohen","sequence":"additional","affiliation":[{"name":"University of Missouri\u2013Kansas City School of Medicine (D.J.C., E.A.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Giugliano","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Brigham and Women\u2019s Hospital, Boston, MA (E.M.A., C.T.R., E.B., R.P.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8631-6211","authenticated-orcid":true,"given":"Elizabeth A.","family":"Magnuson","sequence":"additional","affiliation":[{"name":"University of Missouri\u2013Kansas City School of Medicine (D.J.C., E.A.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the ENGAGE AF-TIMI 48 Trial 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