{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T12:10:46Z","timestamp":1780488646699,"version":"3.54.1"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,11,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) demonstrated that antiplatelet therapy with rivaroxaban 2.5\u2009mg twice daily compared with placebo reduced the first event in a composite end point in patients with peripheral artery disease after revascularization. The purpose of this analysis was to (1) evaluate whether rivaroxaban decreased the most severe events and (2) compare the harm and benefit of rivaroxaban on the same scale.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">Two exploratory, hierarchical analyses of the primary efficacy composite outcome and one exploratory analysis of the net clinical benefit composite outcome were prespecified. The global rank method and the win ratio method ranked components of the composite outcome by clinical importance. The net clinical benefit included both efficacy and safety outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      The global rank method demonstrated that participants on rivaroxaban had fewer or later events than their placebo counterparts when events were compared in a hierarchical manner (primary ranking,\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.0158). The win ratio approach demonstrated fewer or later fatal and nonfatal ischemic events in the rivaroxaban arm (win ratio, 1.16 [95% CI, 1.03\u20131.30];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.0167). The net clinical benefit analysis revealed an overall beneficial effect of rivaroxaban when different efficacy and safety end points were included (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Evaluation of the VOYAGER PAD primary outcome exploring ranking of components revealed that (1) rivaroxaban decreased the most severe ischemic events and (2) that across different efficacy and safety outcomes, results consistently supported a favorable benefit\u2013risk profile. These results help inform shared decision making on the use of rivaroxaban 2.5 mg twice daily with daily antiplatelet therapy.<\/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=\"http:\/\/clinicaltrials.gov\/\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; unique identifier: NCT02504216.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.039752","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T10:55:39Z","timestamp":1761216939000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Rivaroxaban in Peripheral Artery Disease After Revascularization: Worst Events and Net Outcomes in VOYAGER PAD"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1072-557X","authenticated-orcid":false,"given":"Shea","family":"Hogan","sequence":"first","affiliation":[{"name":"CPC Clinical Research","place":["Aurora, USA"]},{"name":"Denver Health","place":["Denver, USA"]},{"name":"University of Colorado","place":["Aurora, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0046-0264","authenticated-orcid":false,"given":"Michael","family":"Szarek","sequence":"additional","affiliation":[{"name":"CPC Clinical Research","place":["Aurora, USA"]},{"name":"Downstate Health Sciences University School of Public Health","place":["Brooklyn, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5664-6439","authenticated-orcid":false,"given":"E. Sebastian","family":"Debus","sequence":"additional","affiliation":[{"name":"University Heart & Vascular Center Hamburg\u2010Eppendorf","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1012-7307","authenticated-orcid":false,"given":"Mark","family":"Nehler","sequence":"additional","affiliation":[{"name":"CPC Clinical Research","place":["Aurora, USA"]},{"name":"University of Colorado","place":["Aurora, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3692-7441","authenticated-orcid":false,"given":"Sonia S.","family":"Anand","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, McMaster University and Hamilton Health Sciences","place":["Hamilton, Canada"]}],"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, Duke University","place":["Durham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2161-3151","authenticated-orcid":false,"given":"Akos Ferenc","family":"Pap","sequence":"additional","affiliation":[{"name":"Bayer AG","place":["Wuppertal, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiaowei","family":"Deng","sequence":"additional","affiliation":[{"name":"Janssen Research & Development","place":["Raritan, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Hodge","sequence":"additional","affiliation":[{"name":"Bayer AG","place":["Wuppertal, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2468-2523","authenticated-orcid":false,"given":"Lloyd P.","family":"Haskell","sequence":"additional","affiliation":[{"name":"Janssen Research & Development","place":["Raritan, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8213-232X","authenticated-orcid":false,"given":"Eva","family":"Muehlhofer","sequence":"additional","affiliation":[{"name":"Bayer AG","place":["Wuppertal, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9428-4408","authenticated-orcid":false,"given":"Scott E.","family":"Berkowitz","sequence":"additional","affiliation":[{"name":"CPC Clinical Research","place":["Aurora, USA"]},{"name":"University of Colorado","place":["Aurora, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6192-1741","authenticated-orcid":false,"given":"Rupert M.","family":"Bauersachs","sequence":"additional","affiliation":[{"name":"Frankfurt, and Center for Thrombosis and Hemostasis, University of Mainz","place":["Mainz, Germany"]}],"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","place":["Aurora, USA"]},{"name":"University of Colorado","place":["Aurora, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001005"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2000052"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2018.01.011"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab390"},{"key":"e_1_3_1_6_2","unstructured":"U.S. Food & Drug Administration . Approval letter rivaroxaban. 2021. Accessed April 3 2024. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/appletter\/2021\/022406Orig1s037;%20202439Orig1s035ltr.pdf."},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2022.02.029"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-149-9-200811040-00004"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2012.07.002"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.2307\/2531158"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2008.01.009"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.109.926030"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/pst.2251"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr352"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/biom.12225"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa665"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i6"},{"key":"e_1_3_1_18_2","first-page":"351","article-title":"On the combination of independent two\u2010sample tests of Wilcoxon","volume":"37","author":"Van Elteren PH","year":"1960","unstructured":"Van Elteren PH. On the combination of independent two\u2010sample tests of Wilcoxon. Bull Int Stat Inst. 1960;37:351\u2013361.","journal-title":"Bull Int Stat Inst"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19990615)18:11<1341::AID-SIM129>3.0.CO;2-7"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.19.2554"},{"key":"e_1_3_1_21_2","first-page":"1905","article-title":"International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH harmonized tripartite guidelines: statistical principles for clinical trials","volume":"18","author":"ICH Expert Working Group","year":"1999","unstructured":"ICH Expert Working Group . International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH harmonized tripartite guidelines: statistical principles for clinical trials. Stat Med. 1999;18:1905\u20131942.","journal-title":"Stat Med"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c3920"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/ehjacc\/zuac168"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.11919\/j.issn.1002-0829.217011"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2020.05.011"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.8967"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.29"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu262"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2016.08.009"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw543"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.4244\/EIJ-D-16-00745"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1805689"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2020.02.010"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2206286"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.2853"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2022.107040"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-151-5-200909010-00003"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.013525"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11239-022-02717-2"},{"key":"e_1_3_1_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2023.117395"},{"key":"e_1_3_1_41_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.046048"},{"key":"e_1_3_1_42_2","unstructured":"Shen D Lu Z. Computation of correlation coefficient and its confidence interval in SAS. Accessed April 20 2025. https:\/\/support.sas.com\/resources\/papers\/proceedings\/proceedings\/sugi31\/170\u201031.pdf."},{"key":"e_1_3_1_43_2","first-page":"3","article-title":"On the \u2018probable error\u2019 of a coefficient of correlation deduced from a small sample (PDF)","volume":"1","author":"Fisher RA","year":"1921","unstructured":"Fisher RA. On the \u2018probable error\u2019 of a coefficient of correlation deduced from a small sample (PDF). Metron. 1921;1:3\u201332.","journal-title":"Metron"},{"key":"e_1_3_1_44_2","unstructured":"Wicklin R. Fisher's transformation of the correlation coefficient. 2017. Accessed June 5 2025. https:\/\/blogs.sas.com\/content\/iml\/2017\/09\/20\/fishers\u2010transformation\u2010correlation.html."}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.124.039752","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:20:15Z","timestamp":1780485615000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.124.039752"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,4]]},"references-count":43,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2025,11,4]]}},"alternative-id":["10.1161\/JAHA.124.039752"],"URL":"https:\/\/doi.org\/10.1161\/jaha.124.039752","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,4]]},"assertion":[{"value":"2025-03-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e039752"}}