{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:02:10Z","timestamp":1789826530519,"version":"4.0.1"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2021,10,5]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Patients with peripheral artery disease requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) demonstrated that rivaroxaban significantly reduced this risk. The efficacy and safety of rivaroxaban has not been described in patients who underwent surgical LER.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>The VOYAGER PAD trial randomized patients with peripheral artery disease after surgical and endovascular LER to rivaroxaban 2.5 mg twice daily plus aspirin or matching placebo plus aspirin and followed for a median of 28 months. The primary end point was a composite of acute limb ischemia, major vascular amputation, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction major bleeding. International Society on Thrombosis and Haemostasis bleeding was a secondary safety outcome. All efficacy and safety outcomes were adjudicated by a blinded independent committee.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Of the 6564 randomized, 2185 (33%) underwent surgical LER and 4379 (67%) endovascular. Compared with placebo, rivaroxaban reduced the primary end point consistently regardless of LER method (\n              <jats:italic>P<\/jats:italic>\n              -interaction, 0.43). After surgical LER, the primary efficacy outcome occurred in 199 (18.4%) patients in the rivaroxaban group and 242 (22.0%) patients in the placebo group with a cumulative incidence at 3 years of 19.7% and 23.9%, respectively (hazard ratio, 0.81 [95% CI, 0.67\u20130.98];\n              <jats:italic>P<\/jats:italic>\n              =0.026). In the overall trial, Thrombolysis in Myocardial Infarction major bleeding and International Society on Thrombosis and Haemostasis major bleeding were increased with rivaroxaban. There was no heterogeneity for Thrombolysis in Myocardial Infarction major bleeding (\n              <jats:italic>P<\/jats:italic>\n              -interaction, 0.17) or International Society on Thrombosis and Haemostasis major bleeding (\n              <jats:italic>P<\/jats:italic>\n              -interaction, 0.73) on the basis of the LER approach. After surgical LER, the principal safety outcome occurred in 11 (1.0%) patients in the rivaroxaban group and 13 (1.2%) patients in the placebo group; 3-year cumulative incidence was 1.3% and 1.4%, respectively (hazard ratio, 0.88 [95% CI, 0.39\u20131.95];\n              <jats:italic>P<\/jats:italic>\n              =0.75) Among surgical patients, the composite of fatal bleeding or intracranial hemorrhage (\n              <jats:italic>P<\/jats:italic>\n              =0.95) and postprocedural bleeding requiring intervention (\n              <jats:italic>P<\/jats:italic>\n              =0.93) was not significantly increased.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>The efficacy of rivaroxaban is associated with a benefit in patients who underwent surgical LER. Although bleeding was increased with rivaroxaban plus aspirin, the incidence was low, with no significant increase in fatal bleeding, intracranial hemorrhage, or postprocedural bleeds requiring intervention.<\/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=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique Identifier: NCT02504216.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.121.054835","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T09:00:15Z","timestamp":1628758815000},"page":"1104-1116","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":47,"title":["Effect of Rivaroxaban and Aspirin in Patients With Peripheral Artery Disease Undergoing Surgical Revascularization: Insights From the VOYAGER PAD Trial"],"prefix":"10.1161","volume":"144","clinical-trial-number":[{"clinical-trial-number":"nct02504216","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5664-6439","authenticated-orcid":true,"given":"E. Sebastian","family":"Debus","sequence":"first","affiliation":[{"name":"Department of Vascular Medicine, Vascular Surgery\u2013Angiology\u2013Endovascular Therapy, University of Hamburg-Eppendorf, Hamburg, Germany (E.S.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Nehler","sequence":"additional","affiliation":[{"name":"CPC Clinical Research, Aurora, CO (M.R.N., N.G., W.H.C., T.B., N.J., C.N.H., W.R.H., M.P.B.)."},{"name":"Division of Vascular Surgery, Department of Surgery (M.R.N., N.G.), Department of Medicine, University of Colorado School of Medicine, Aurora."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9410-4094","authenticated-orcid":true,"given":"Nicholas","family":"Govsyeyev","sequence":"additional","affiliation":[{"name":"CPC Clinical Research, Aurora, CO (M.R.N., N.G., W.H.C., T.B., N.J., C.N.H., W.R.H., M.P.B.)."},{"name":"Division of Vascular Surgery, Department of Surgery (M.R.N., N.G.), Department of Medicine, University of Colorado School of Medicine, Aurora."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupert M.","family":"Bauersachs","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Klinikum Darmstadt, Darmstadt, and Center for Thrombosis and Hemostasis, University of Mainz, Germany (R.M.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia S.","family":"Anand","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, Hamilton Health Sciences and McMaster University, Ontario, Canada (S.S.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2393-0855","authenticated-orcid":true,"given":"Manesh R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Division of Cardiology, Duke University, Durham, NC (M.R.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5273-0609","authenticated-orcid":true,"given":"Fabrizio","family":"Fanelli","sequence":"additional","affiliation":[{"name":"Vascular and Interventional Radiology Department, Careggi University Hospital, University of Florence, Italy (F.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren H.","family":"Capell","sequence":"additional","affiliation":[{"name":"CPC Clinical Research, Aurora, CO (M.R.N., N.G., W.H.C., T.B., N.J., C.N.H., W.R.H., M.P.B.)."},{"name":"Division of Endocrinology (W.H.C.), Department of Medicine, University of Colorado School of Medicine, Aurora."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Brackin","sequence":"additional","affiliation":[{"name":"CPC Clinical Research, Aurora, CO (M.R.N., N.G., W.H.C., T.B., N.J., C.N.H., W.R.H., M.P.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Hinterreiter","sequence":"additional","affiliation":[{"name":"Department for Vascular Surgery Krankenhaus Barmherzige Br\u00fcder Linz, Austria (F.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dainis","family":"Krievins","sequence":"additional","affiliation":[{"name":"Pauls Stradins University Hospital, University of Latvia, Riga (D.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Nault","sequence":"additional","affiliation":[{"name":"Vascular and Endovascular Surgery, McGill University Montreal, Quebec, Canada (P.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9906-4658","authenticated-orcid":true,"given":"Gabriele","family":"Piffaretti","sequence":"additional","affiliation":[{"name":"Vascular Surgery, Department of Medicine and Surgery, University of Insubria School of Medicine, Varese, Italy (G.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexei","family":"Svetlikov","sequence":"additional","affiliation":[{"name":"The I.I. Mechnikov North-Western State Medical University, Department of Cardiovascular Surgery, St. Petersburg, Russia (A.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Jaeger","sequence":"additional","affiliation":[{"name":"CPC Clinical Research, Aurora, CO (M.R.N., N.G., W.H.C., T.B., N.J., C.N.H., W.R.H., M.P.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie N.","family":"Hess","sequence":"additional","affiliation":[{"name":"CPC Clinical Research, Aurora, CO (M.R.N., N.G., W.H.C., T.B., N.J., C.N.H., W.R.H., M.P.B.)."},{"name":"Division of Cardiology (C.N.H., W.R.H., M.P.B.), Department of Medicine, University of Colorado School of Medicine, Aurora."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik H.","family":"Sillesen","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Rigshospitalet, Institute of Clinical Medicine, University of Copenhagen, Denmark (H.H.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Conte","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, University of California, San Francisco (M.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4955-4384","authenticated-orcid":true,"given":"Joseph","family":"Mills","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery and Endovascular Therapy, Baylor College of Medicine, Houston, TX (J.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Muehlhofer","sequence":"additional","affiliation":[{"name":"Bayer, Wuppertal, Germany (E.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lloyd P.","family":"Haskell","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Raritan, NJ (L.P.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Berkowitz","sequence":"additional","affiliation":[{"name":"Thrombosis Group Head, Clinical Development, Bayer US, Whippany, NJ (S.D.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Hiatt","sequence":"additional","affiliation":[{"name":"CPC Clinical Research, Aurora, CO (M.R.N., N.G., W.H.C., T.B., N.J., C.N.H., W.R.H., M.P.B.)."},{"name":"Division of Cardiology (C.N.H., W.R.H., M.P.B.), Department of Medicine, University of Colorado School of Medicine, Aurora."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc P.","family":"Bonaca","sequence":"additional","affiliation":[{"name":"CPC Clinical Research, Aurora, CO (M.R.N., N.G., W.H.C., T.B., N.J., C.N.H., W.R.H., M.P.B.)."},{"name":"Division of Cardiology (C.N.H., W.R.H., M.P.B.), Department of Medicine, University of Colorado School of Medicine, Aurora."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2016.179"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.11-2307"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.07.768"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr211"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.11.008"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2006.12.037"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2017.01.067"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.039773"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67704-5"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2005.12.058"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2009.09.044"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1080\/09537100600746540"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejvs.2003.10.015"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-200103000-00021"},{"key":"e_1_3_6_16_2","first-page":"78","article-title":"Mechanisms of vein graft failure: the location, distribution, and characteristics of lesions that predispose to graft failure.","volume":"6","author":"Mills JL","year":"1993","unstructured":"Mills, JL. 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