{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T08:02:52Z","timestamp":1781164972968,"version":"3.54.1"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,4,16]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">The 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) trial compared rivaroxaban (2.5\u2009mg twice a day) plus aspirin with\u00a0aspirin alone in patients with symptomatic peripheral artery disease requiring endovascular or surgical limb revascularization, with 50% receiving clopidogrel background therapy. The New Drug Indication application includes benefit\u2013risk assessments using clinical judgment to balance benefits against risks. During its review, the US Food and Drug Administration requested additional quantitative benefit\u2013risk analyses with formal weighting approaches.<\/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\">Benefits and risks were assessed using rate differences between treatment groups (unweighted analysis). To account for clinical importance of the end points, a multi\u2010criteria decision analysis was conducted using health state utility values as weights. Monte Carlo simulations incorporated statistical uncertainties of the event rates and utility weights. Intent\u2010to\u2010treat and on\u2010treatment analyses were conducted. For unweighted intent\u2010to\u2010treat analyses, rivaroxaban plus aspirin would result in 120 (95% CI, \u2212208 to \u221232) fewer events of the primary composite end point (per 10\u2009000 patient\u2010years) compared with aspirin alone. Rivaroxaban caused an excess of 40 (95% CI, 8\u201372) Thrombolysis in Myocardial Infarction major bleeding events, which was largely driven by nonfatal, nonintracranial hemorrhage Thrombolysis in Myocardial Infarction major bleeding events. For weighted analyses, rivaroxaban resulted in the utility equivalent of 13.7 (95% CI, \u221285.3 to 52.6) and 68.1 (95% CI, 7.9\u2013135.7) fewer deaths per 10\u2009000 patient\u2010years (intent\u2010to\u2010treat and on\u2010treatment, respectively), corresponding to probabilities of 64.4% and 98.7%, respectively, that benefits outweigh risks favoring rivaroxaban per Monte Carlo simulation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">These analyses show a favorable benefit\u2013risk profile of rivaroxaban therapy in the VOYAGER PAD trial, with findings generally consistent between the unweighted and weighted approaches.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.032782","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T13:46:48Z","timestamp":1712065608000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Quantitative Benefit\u2013Risk Evaluation of Rivaroxaban in Patients After Peripheral Arterial Revascularization: The VOYAGER PAD Trial"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5824-2040","authenticated-orcid":false,"given":"Zhong","family":"Yuan","sequence":"first","affiliation":[{"name":"Janssen Research &amp; Development LLC Horsham PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9069-8446","authenticated-orcid":false,"given":"Bennett","family":"Levitan","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development LLC Titusville NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiaowei","family":"Deng","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development LLC Horsham PA"}],"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, Department of Medicine University of Colorado Aurora CO"}],"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":"Cardioangiologisches Centrum Bethanien \u2010 CCB Gef\u00e4\u00df\u2010Centrum Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9428-4408","authenticated-orcid":false,"given":"Scott D.","family":"Berkowitz","sequence":"additional","affiliation":[{"name":"CPC Clinical Research, Department of Medicine University of Colorado Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2468-2523","authenticated-orcid":false,"given":"Lloyd","family":"Haskell","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development LLC Horsham PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7744-1486","authenticated-orcid":false,"given":"Elliot S.","family":"Barnathan","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development LLC Horsham PA"}],"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, Department of Medicine University of Colorado Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD010835.pub2"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61249-0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amepre.2006.12.010"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000659"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.03.524"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.019355"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.039773"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2006.12.037"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.11.050"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1177\/0003319720936505"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000470"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz425"},{"key":"e_1_3_2_14_2","unstructured":"ClinicalTrials.gov Identifier: NCT01776424. 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