{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T19:03:57Z","timestamp":1780513437821,"version":"3.54.1"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Interventions"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Patients with peripheral artery disease (PAD) undergoing lower extremity revascularization (LER) are at high risk of major adverse limb events (MALE) and major adverse cardiovascular events. The VOYAGER-PAD trial (Vascular Outcomes Study of Acetylsalicylic Acid Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) demonstrated that rivaroxaban 2.5 mg twice daily on top of antiplatelet therapy significantly reduced this risk. Whether the risk of major adverse cardiovascular events and MALE and the effect of rivaroxaban are consistent in patients with a history of prior LER versus those without has not been described.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>VOYAGER-PAD randomized patients with symptomatic PAD undergoing LER to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily. The history of prior LER was collected at baseline. The primary end point was a composite of acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction major bleeding.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      A total of 6564 patients were enrolled with 2336 (35.5%) having a prior history of LER. Patients with a history of prior LER had a higher rate of MALE relative to those without prior LER (3-year Kaplan-Meier cumulative rates, 12.9% versus 8.0%; hazard ratio [HR], 1.58 [95% CI, 1.25\u20131.99]). Compared with placebo, rivaroxaban reduced the primary efficacy end point with a numerically greater relative benefit in those with (HR, 0.73 [95% CI, 0.60\u20130.88]) versus without prior LER (HR, 0.94 [95% CI, 0.81\u20131.10];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      <jats:sub>interaction<\/jats:sub>\n                      =0.036). The relative increase in Thrombolysis in Myocardial Infarction major bleeding with rivaroxaban was consistent regardless of prior LER status (prior LER: HR, 1.08 [95% CI, 0.62\u20131.89]; no prior LER: HR, 1.88 [95% CI, 1.09\u20133.25];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      <jats:sub>interaction<\/jats:sub>\n                      =0.16).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Patients with PAD with prior LER are at particularly high risk of MALE relative to those presenting without prior LER. Rivaroxaban reduces the risk of major adverse cardiovascular events and MALE after LER for symptomatic PAD with a greater relative benefit in those with prior LER.<\/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: NCT02504216.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circinterventions.125.015229","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T10:00:11Z","timestamp":1772186411000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Low-Dose Rivaroxaban Plus Aspirin in Patients With PAD Undergoing Lower Extremity Revascularization With and Without History of Prior Limb Revascularization: Insight From the VOYAGER-PAD Trial"],"prefix":"10.1161","volume":"19","clinical-trial-number":[{"clinical-trial-number":"nct02504216","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Mario Enrico","family":"Canonico","sequence":"first","affiliation":[{"name":"CPC Clinical Research, Aurora, CO (M.E.C., M.R.N., C.N.H., W.H.C., J.Y., J.C., M. Szarek, S.D.B., M.P.B.)."},{"name":"Division of Cardiology, Department of Medicine (M.E.C., C.N.H., M. Szarek, S.D.B., M.P.B.), University of Colorado School of Medicine, Aurora."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Parr","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Heart of the Rockies, Salida, CO (J.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5664-6439","authenticated-orcid":true,"given":"E. Sebastian","family":"Debus","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Vascular Surgery-Angiology-Endovascular Therapy, University of Hamburg-Eppendorf, Germany (E.S.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Nehler","sequence":"additional","affiliation":[{"name":"CPC Clinical Research, Aurora, CO (M.E.C., M.R.N., C.N.H., W.H.C., J.Y., J.C., M. Szarek, S.D.B., M.P.B.)."},{"name":"Department of Surgery (M.R.N.), University of Colorado School of Medicine, Aurora."}],"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":"Division of Cardiology, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (M.R.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3692-7441","authenticated-orcid":true,"given":"Sonia S.","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Medicine, Population Health Research Institute, Hamilton Health Sciences, McMaster University, ON, Canada (S.S.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Svet","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis (M. Svet)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5830-0511","authenticated-orcid":true,"given":"Connie N.","family":"Hess","sequence":"additional","affiliation":[{"name":"CPC Clinical Research, Aurora, CO (M.E.C., M.R.N., C.N.H., W.H.C., J.Y., J.C., M. Szarek, S.D.B., M.P.B.)."},{"name":"Division of Cardiology, Department of Medicine (M.E.C., C.N.H., M. Szarek, S.D.B., M.P.B.), University of Colorado School of Medicine, Aurora."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren H.","family":"Capell","sequence":"additional","affiliation":[{"name":"CPC Clinical Research, Aurora, CO (M.E.C., M.R.N., C.N.H., W.H.C., J.Y., J.C., M. Szarek, S.D.B., M.P.B.)."},{"name":"Division of Endocrinology, Department of Medicine (W.H.C.), University of Colorado School of Medicine, Aurora."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Ycas","sequence":"additional","affiliation":[{"name":"CPC Clinical Research, Aurora, CO (M.E.C., M.R.N., C.N.H., W.H.C., J.Y., J.C., M. Szarek, S.D.B., M.P.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Chen","sequence":"additional","affiliation":[{"name":"CPC Clinical Research, Aurora, CO (M.E.C., M.R.N., C.N.H., W.H.C., J.Y., J.C., M. Szarek, S.D.B., M.P.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0046-0264","authenticated-orcid":true,"given":"Michael","family":"Szarek","sequence":"additional","affiliation":[{"name":"CPC Clinical Research, Aurora, CO (M.E.C., M.R.N., C.N.H., W.H.C., J.Y., J.C., M. Szarek, S.D.B., M.P.B.)."},{"name":"Division of Cardiology, Department of Medicine (M.E.C., C.N.H., M. Szarek, S.D.B., M.P.B.), University of Colorado School of Medicine, Aurora."},{"name":"State University of New York, Downstate Health Sciences University, Brooklyn (M. Szarek)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8213-232X","authenticated-orcid":true,"given":"Eva","family":"Muehlhofer","sequence":"additional","affiliation":[{"name":"Bayer AG Research and Development, Pharmaceuticals, Wuppertal, Germany (E.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2468-2523","authenticated-orcid":true,"given":"Lloyd P.","family":"Haskell","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Raritan, NJ (L.P.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9428-4408","authenticated-orcid":true,"given":"Scott D.","family":"Berkowitz","sequence":"additional","affiliation":[{"name":"CPC Clinical Research, Aurora, CO (M.E.C., M.R.N., C.N.H., W.H.C., J.Y., J.C., M. Szarek, S.D.B., M.P.B.)."},{"name":"Division of Cardiology, Department of Medicine (M.E.C., C.N.H., M. Szarek, S.D.B., M.P.B.), University of Colorado School of Medicine, Aurora."},{"name":"Division of Hematology, Department of Medicine (S.D.B.), University of Colorado School of Medicine, Aurora."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6192-1741","authenticated-orcid":true,"given":"Rupert M.","family":"Bauersachs","sequence":"additional","affiliation":[{"name":"Cardioangiologic Center, Agaplesion Bethanien Hospital, Frankfurt am Main, Germany (R.M.B.)."},{"name":"Center for Thrombosis and Hemostasis, University of Mainz, Germany (R.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9860-3584","authenticated-orcid":true,"given":"Marc P.","family":"Bonaca","sequence":"additional","affiliation":[{"name":"CPC Clinical Research, Aurora, CO (M.E.C., M.R.N., C.N.H., W.H.C., J.Y., J.C., M. Szarek, S.D.B., M.P.B.)."},{"name":"Division of Cardiology, Department of Medicine (M.E.C., C.N.H., M. 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