{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:34:33Z","timestamp":1790883273251,"version":"4.1.0"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer AG","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005205","name":"Janssen Research & Development, LLC","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Tier 1 Canada Research Chair in Ethnicity and Cardiovascular Disease"},{"name":"Michael G. DeGroote Heart and Stroke Foundation Chair in Population Health"},{"name":"Jack Hirsh Population Health Research Institute Chair in Thrombosis Research"},{"name":"Heart & Stroke Foundation\/Marion W. Burke Chair in Cardiovascular Disease"},{"name":"William R. Hiatt Chair in Cardiovascular Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Peripheral artery disease (PAD) patients suffer a high risk of major cardiovascular (CV) events, with athero-thrombo-embolism as the underlying pathophysiologic mechanism. Recently, two large randomized clinical trials evaluated the efficacy and safety of low-dose rivaroxaban twice daily plus aspirin in stable PAD outpatients and those immediately after peripheral revascularization. We sought to determine if the effects of low-dose rivaroxaban and aspirin compared to aspirin alone are consistent across this broad spectrum of PAD patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We conducted a random-effects meta-analysis of the COMPASS and VOYAGER randomized trials among 11 560 PAD patients (4996 from COMPASS and 6564 from VOYAGER) in the primary analysis and 9332 (2768 from COMPASS and 6564 from VOYAGER) with lower extremity (LE)-PAD in the secondary analysis. The hazard ratio (HR) for the composite of CV death, myocardial infarction, ischaemic stroke, acute limb ischaemia, or major vascular amputation was 0.79 (95% confidence interval, CI: 0.65\u20130.95) comparing low-dose rivaroxaban plus aspirin to aspirin alone. While the risk of major bleeding was increased with low-dose rivaroxaban plus aspirin compared to aspirin alone [HR: 1.51 (95% CI: 1.22\u20131.87)], there was no significant increase in severe bleeding [HR: 1.18 (95% CI: 0.79\u20131.76)]. Similar effects were observed in the subset with symptomatic LE-PAD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Among PAD patients, low-dose rivaroxaban plus aspirin is superior to aspirin alone in reducing CV and limb outcomes including acute limb ischaemia and major vascular amputation. This reduction is offset by a relative increase in major bleeding, but not by an excess of fatal or critical organ bleeding. The consistency of findings of these trials supports the use of combination low-dose rivaroxaban plus aspirin in PAD patients across a broad spectrum of disease.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwab128","type":"journal-article","created":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T03:14:50Z","timestamp":1626491690000},"page":"e181-e189","source":"Crossref","is-referenced-by-count":34,"title":["Low-dose rivaroxaban and aspirin among patients with peripheral artery disease: a meta-analysis of the COMPASS and VOYAGER trials"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3692-7441","authenticated-orcid":false,"given":"Sonia S","family":"Anand","sequence":"first","affiliation":[{"name":"Department of Medicine, McMaster University, 1280 Main St West, Hamilton, ON L8S 4L8, Canada"},{"name":"Population Health Research Institute, Hamilton Health Sciences, 237 Barton St East, Hamilton, ON L8L 2X2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Will","family":"Hiatt","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Colorado School of Medicine, 13001 E 17th Pl, Boulder, Colorado 80045, \u00a0USA"},{"name":"Colorado Prevention Center (CPC) Clinical Research, 2115 N Scranton St., Suite 2040, Aurora, Colorado 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanne","family":"Dyal","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, Hamilton Health Sciences, 237 Barton St East, Hamilton, ON L8L 2X2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6192-1741","authenticated-orcid":false,"given":"Rupert","family":"Bauersachs","sequence":"additional","affiliation":[{"name":"AGAPLESION Bethanien Krankenhaus Im Pr\u00fcfling 23 D-60389, Frankfurt,\u00a0Germany"},{"name":"Center for Thrombosis and Hemostasis, University of Mainz, Langenbeckstrasse 1, 55131 Mainz, 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":"University of Colorado School of Medicine, 13001 E 17th Pl, Boulder, Colorado 80045,\u00a0USA"},{"name":"Colorado Prevention Center (CPC) Clinical Research, 2115 N Scranton St.\u2002, Suite 2040, Aurora, Colorado 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2362-6498","authenticated-orcid":false,"given":"Kelley R H","family":"Branch","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of Washington Medical Center, 1959 N.E. Pacific St., Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Debus","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, University of Hamburg-Eppendorf, Martinistra\u00dfe 52, 20246, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0140-2752","authenticated-orcid":false,"given":"Keith A A","family":"Fox","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Emergency, National Center for Cardiovascular Disease and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xicheng District, Beijing 100037, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Muehlhofer","sequence":"additional","affiliation":[{"name":"Research and Development, Pharmaceuticals, Bayer AG, Friedrich-Ebert-Stra\u00dfe 217\/333, 42117 Wuppertal, 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":"Department of Cardiology, University of Colorado School of Medicine, 13001 E 17th Pl, Boulder, Colorado 80045, \u00a0USA"},{"name":"Department of Vascular Surgery, University Of Colorado School Of Medicine, 13100 E Colfax Ave, Suite 70, Aurora, CO 80011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lloyd P","family":"Haskell","sequence":"additional","affiliation":[{"name":"JANSSEN Research & Development, LLC, 920 US-202, Raritan, NJ 08869, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manesh","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Clinical Pharmacology, Duke University School Of Medicine, 2301 Erwin Road, Hafs Building, Room 8695, Durham, NC 27710, 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":"Colorado Prevention Center (CPC) Clinical Research, 2115 N Scranton St., Suite 2040, Aurora, Colorado 80045, USA"},{"name":"University of Colorado School of Medicine, 13001 E 17th Pl, Boulder, Colorado 80045,\u00a0USA"},{"name":"SUNY Downstate Health Sciences University, Brooklyn, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim","family":"Yusuf","sequence":"additional","affiliation":[{"name":"Department of Medicine, McMaster University, 1280 Main St West, Hamilton, ON L8S 4L8, Canada"},{"name":"Population Health Research Institute, Hamilton Health Sciences, 237 Barton St East, Hamilton, ON L8L 2X2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4126-1285","authenticated-orcid":false,"given":"John","family":"Eikelboom","sequence":"additional","affiliation":[{"name":"Department of Medicine, McMaster University, 1280 Main St West, Hamilton, ON L8S 4L8, Canada"},{"name":"Population Health Research Institute, Hamilton Health Sciences, 237 Barton St East, Hamilton, ON L8L 2X2, Canada"}],"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":"Department of Cardiology, University of Colorado School of Medicine, 13001 E 17th Pl, Boulder, Colorado 80045, \u00a0USA"},{"name":"Colorado Prevention Center (CPC) Clinical Research, 2115 N Scranton St., Suite 2040, Aurora, Colorado 80045, USA"},{"name":"Division of Cardiovascular Medicine, University of Colorado Anschutz School of Medicine, 13001 East 17th Place, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"key":"2022050522134462100_zwab128-B1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/nrcardio.2016.179","article-title":"Peripheral artery disease: epidemiology and global perspectives","volume":"14","author":"Fowkes","year":"2017","journal-title":"Nat Rev Cardiol"},{"key":"2022050522134462100_zwab128-B2","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.jacc.2018.06.041","article-title":"Major adverse limb events and 1-year outcomes after peripheral artery revascularization","volume":"72","author":"Hess","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"2022050522134462100_zwab128-B3","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1016\/j.jacc.2018.03.008","article-title":"Major adverse limb events and mortality in patients with peripheral artery disease: the COMPASS Trial","volume":"71","author":"Anand","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"2022050522134462100_zwab128-B4","first-page":"e686","article-title":"2016 AHA\/ACC Guideline on the management of patients with lower extremity peripheral artery disease: executive summary: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"135","author":"Gerhard-Herman","year":"2017","journal-title":"Circulation"},{"key":"2022050522134462100_zwab128-B5","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1093\/eurheartj\/ehx095","article-title":"2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed by: the European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS)","volume":"39","author":"Aboyans","year":"2018","journal-title":"Eur Heart J"},{"key":"2022050522134462100_zwab128-B6","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.cjca.2017.06.001","article-title":"Rationale, design and baseline characteristics of participants in the cardiovascular outcomes for people using anticoagulation strategies (COMPASS) trial","volume":"33","author":"Bosch","year":"2017","journal-title":"Can J Cardiol"},{"key":"2022050522134462100_zwab128-B7","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ahj.2018.01.011","article-title":"Rationale and design for the Vascular Outcomes study of ASA along with rivaroxaban in endovascular or surgical limb revascularization for peripheral artery disease (VOYAGER PAD)","volume":"199","author":"Capell","year":"2018","journal-title":"Am Heart J"},{"key":"2022050522134462100_zwab128-B8","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0140-6736(17)32409-1","article-title":"Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial","volume":"391","author":"Anand","year":"2018","journal-title":"Lancet"},{"key":"2022050522134462100_zwab128-B9","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1056\/NEJMoa2000052","article-title":"Rivaroxaban in peripheral artery disease after revascularization","volume":"382","author":"Bonaca","year":"2020","journal-title":"N Engl J Med"},{"key":"2022050522134462100_zwab128-B10","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1056\/NEJMoa1709118","article-title":"Rivaroxaban with or without aspirin in stable cardiovascular disease","volume":"377","author":"Eikelboom","year":"2017","journal-title":"N Engl J Med"},{"key":"2022050522134462100_zwab128-B11","first-page":"21","article-title":"Rivaroxaban and aspirin in patients with symptomatic lower extremity peripheral artery disease: a subanalysis of the COMPASS randomized clinical trial","volume":"6","author":"Kaplovitch","year":"2021","journal-title":"JAMA Cardiol"},{"key":"2022050522134462100_zwab128-B12","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/j.1538-7836.2009.03678.x","article-title":"Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients","volume":"8","author":"Schulman","year":"2010","journal-title":"J Thromb Haemost"},{"key":"2022050522134462100_zwab128-B13","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"DerSimonian","year":"1986","journal-title":"Control Clin Trials"},{"key":"2022050522134462100_zwab128-B14","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"Higgins","year":"2003","journal-title":"BMJ"},{"key":"2022050522134462100_zwab128-B15","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1001\/jama.282.21.2058","article-title":"Oral anticoagulant therapy in patients with coronary artery disease: a meta-analysis","volume":"282","author":"Anand","year":"1999","journal-title":"JAMA"},{"key":"2022050522134462100_zwab128-B16","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.ahj.2020.01.015","article-title":"Xarelto plus Acetylsalicylic acid: Treatment patterns and Outcomes in patients with Atherosclerosis (XATOA): Rationale and design of a prospective registry study to assess rivaroxaban 2.5 mg twice daily plus aspirin for prevention of atherothrombotic events in coronary artery disease, peripheral artery disease, or both","volume":"222","author":"Fox","year":"2020","journal-title":"Am Heart J"}],"container-title":["European Journal of Preventive Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eurjpc\/article-pdf\/29\/5\/e181\/43566760\/zwab128.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjpc\/article-pdf\/29\/5\/e181\/43566760\/zwab128.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T22:19:57Z","timestamp":1651789197000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjpc\/article\/29\/5\/e181\/6360030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,31]]},"references-count":16,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,8,31]]},"published-print":{"date-parts":[[2022,5,5]]}},"URL":"https:\/\/doi.org\/10.1093\/eurjpc\/zwab128","relation":{},"ISSN":["2047-4873","2047-4881"],"issn-type":[{"value":"2047-4873","type":"print"},{"value":"2047-4881","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,3,1]]},"published":{"date-parts":[[2021,8,31]]}}}