{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:03:38Z","timestamp":1792191818850,"version":"4.4.0"},"reference-count":75,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peripheral artery disease (PAD) is a major cause of morbidity and mortality but it is usually underdiagnosed and undertreated. Patients with PAD present dysregulated procoagulant, anticoagulant, and fibrinolytic pathways leading to arterial and venous thrombosis. The risk of several ischemic-related complications could be mitigated with appropriate antithrombotic therapy, which plays a central role in all types of PAD. For years, antiplatelets have been indicated in patients with symptomatic PAD or those who have undergone revascularization. Unfortunately, a non-negligible proportion of patients with PAD will suffer from adverse events during the follow-up, even despite proper medical therapies for the prevention of PAD complications. Thus, there is room for improving clinical outcomes in these patients. Given the implication of both, primary and secondary hemostasis in arterial thrombosis and the pathophysiology of PAD, the combination of antiplatelets and anticoagulants has emerged as a potential antithrombotic alternative to antiplatelets alone. In this narrative review article, we have highlighted the most recent evidence about antithrombotic therapy in PAD patients, with a special focus on oral anticoagulation. Certainly, COMPASS and VOYAGER PAD trials have shown promising results. Thus, rivaroxaban in combination with aspirin seem to reduce cardiovascular outcomes with a similar bleeding risk compared to aspirin alone. Nevertheless, results from real-world studies are needed to confirm these observations, and other trials will provide novel evidence about the safety and efficacy of emerging anticoagulant agents.<\/jats:p>","DOI":"10.3390\/ijms22137113","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T12:03:27Z","timestamp":1625141007000},"page":"7113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Antithrombotic Therapy in Patients with Peripheral Artery Disease: A Focused Review on Oral Anticoagulation"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0492-6241","authenticated-orcid":false,"given":"Jos\u00e9 Miguel","family":"Rivera-Caravaca","sequence":"first","affiliation":[{"name":"Department of Cardiology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB-Arrixaca), CIBERCV, 30120 Murcia, Spain"},{"name":"Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool L7 8TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anny","family":"Camelo-Castillo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB-Arrixaca), CIBERCV, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9559-9180","authenticated-orcid":false,"given":"Inmaculada","family":"Ram\u00edrez-Mac\u00edas","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB-Arrixaca), CIBERCV, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Gil-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB-Arrixaca), CIBERCV, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"L\u00f3pez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB-Arrixaca), CIBERCV, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Asunci\u00f3n","family":"Esteve-Pastor","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB-Arrixaca), CIBERCV, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3979-6678","authenticated-orcid":false,"given":"Esteban","family":"Orenes-Pi\u00f1ero","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology-A, University of Murcia, Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB-Arrixaca), CIBERCV, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Tello-Montoliu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB-Arrixaca), CIBERCV, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Mar\u00edn","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB-Arrixaca), CIBERCV, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ejvs.2004.11.001","article-title":"Markers of Coagulation Activation, Endothelial Stimulation and Inflammation in Patients with Peripheral Arterial Disease","volume":"29","author":"Cassar","year":"2005","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1177\/145749691210100204","article-title":"Role and Management of Coagulation Disorders in Peripheral Arterial Disease","volume":"101","author":"Lassila","year":"2012","journal-title":"Scand. J. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1177\/1708538120915997","article-title":"Altered coagulation profile in peripheral artery disease patients","volume":"28","author":"Zamzam","year":"2020","journal-title":"Vascular"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Memtsas, V., Arachchillage, D., and Gorog, D. (2021). Role, Laboratory Assessment and Clinical Relevance of Fibrin, Factor XIII and Endogenous Fibrinolysis in Arterial and Venous Thrombosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031472"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e009584","DOI":"10.1161\/CIRCINTERVENTIONS.120.009584","article-title":"Contemporary Review of Antithrombotic Therapy in Peripheral Artery Disease","volume":"13","author":"Hess","year":"2020","journal-title":"Circ. Cardiovasc. Interv."},{"key":"ref_6","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)","volume":"39","author":"Aboyans","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_7","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":"Gornik","year":"2017","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1016\/j.jvs.2010.10.065","article-title":"ACCF\/AHA\/ACR\/SCAI\/SIR\/SVM\/SVN\/SVS 2010 performance measures for adults with peripheral artery disease: A Report of the American College of Cardiology Foundation\/American Heart Association Task Force on Performance Measures, the American College of Radiology, the Society for Cardiac Angiography and Interventions, the Society for Interventional Radiology, the Society for Vascular Medicine, the Society for Vascular Nursing, and the Society for Vascular Surgery (Writing Committee to Develop Clinical Performance Measures for Peripheral Artery Disease)","volume":"52","author":"Olin","year":"2010","journal-title":"J. Vasc. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/S0140-6736(13)61249-0","article-title":"Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: A systematic review and analysis","volume":"382","author":"Fowkes","year":"2013","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.atherosclerosis.2021.03.019","article-title":"Sex related differences in therapy and outcome of patients with intermittent claudication in a real-world cohort","volume":"325","author":"Makowski","year":"2021","journal-title":"Atherosclerosis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1080\/14779072.2020.1833719","article-title":"Antithrombotic strategies for patients with coronary and lower extremity peripheral artery diseases: A narrative review","volume":"18","author":"Bonaca","year":"2020","journal-title":"Expert Rev. Cardiovasc. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1007\/s12325-019-01132-z","article-title":"Real-World Predictors of Major Adverse Cardiovascular Events and Major Adverse Limb Events Among Patients with Chronic Coronary Artery Disease and\/or Peripheral Arterial Disease","volume":"37","author":"Berger","year":"2020","journal-title":"Adv. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e000697","DOI":"10.1161\/JAHA.113.000697","article-title":"Adherence to Guideline-Recommended Therapy Is Associated With Decreased Major Adverse Cardiovascular Events and Major Adverse Limb Events Among Patients with Peripheral Arterial Disease","volume":"3","author":"Armstrong","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1055\/s-0040-1709711","article-title":"Statins and Major Adverse Limb Events in Patients with Peripheral Artery Disease: A Systematic Review and Meta-Analysis","volume":"120","author":"Pastori","year":"2020","journal-title":"Thromb. Haemost."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3274","DOI":"10.1016\/j.jacc.2018.09.078","article-title":"Cardiovascular and Limb Outcomes in Patients with Diabetes and Peripheral Artery Disease","volume":"72","author":"Wang","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1093\/europace\/euv369","article-title":"Peripheral arterial disease is associated with an increased risk of atrial fibrillation in the elderly","volume":"18","author":"Griffin","year":"2016","journal-title":"Europace"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e13431","DOI":"10.1111\/eci.13431","article-title":"Peripheral artery disease and clinical outcomes in patients with atrial fibrillation: A report from the FANTASIIA registry","volume":"51","author":"Cequier","year":"2021","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ijcard.2017.12.076","article-title":"Relationship of peripheral and coronary artery disease to cardiovascular events in patients with atrial fibrillation","volume":"255","author":"Pastori","year":"2018","journal-title":"Int. J. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ejvs.2010.03.003","article-title":"Prognosis of Atrial Fibrillation in Patients with Symptomatic Peripheral Arterial Disease: Data from the REduction of Atherothrombosis for Continued Health (REACH) Registry","volume":"40","author":"Winkel","year":"2010","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.ahj.2012.12.002","article-title":"High mortality risks after major lower extremity amputation in Medicare patients with peripheral artery disease","volume":"165","author":"Jones","year":"2013","journal-title":"Am. Heart J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ejvs.2011.09.016","article-title":"Two-year Vascular Hospitalisation Rates and Associated Costs in Patients at Risk of Atherothrombosis in France and Germany: Highest Burden for Peripheral Arterial Disease","volume":"43","author":"Smolderen","year":"2012","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/1755-5922.12169","article-title":"The Burden of Major Adverse Cardiac Events and Antiplatelet Prevention in Patients with Coronary or Peripheral Arterial Disease","volume":"34","author":"Khoury","year":"2016","journal-title":"Cardiovasc. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1001\/jama.300.2.197","article-title":"Ankle Brachial Index Combined With Framingham Risk Score to Predict Cardiovascular Events and Mortality: A meta-analysis","volume":"300","author":"Fowkes","year":"2008","journal-title":"JAMA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1161\/ATVBAHA.119.312142","article-title":"Evidence-Based Medical Management of Peripheral Artery Disease","volume":"40","author":"Bevan","year":"2020","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"204","DOI":"10.2174\/1570161117666190206234046","article-title":"Pathophysiology of Thrombosis in Peripheral Artery Disease","volume":"18","author":"Petrucci","year":"2020","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Wiecz\u00f3r, R., Kulwas, A., and Ro\u015b\u0107, D. (2020). Implications of Hemostasis Disorders in Patients with Critical Limb Ischemia\u2014An In-Depth Comparison of Selected Factors. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030659"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1042\/cs1040397","article-title":"Vascular endothelial growth factor and tissue factor in patients with established peripheral artery disease: A link between angiogenesis and thrombogenesis?","volume":"104","author":"Makin","year":"2003","journal-title":"Clin. Sci."},{"key":"ref_28","unstructured":"Chaudhry, R., Usama, S.M., and Babiker, H.M. (2021). Physiology, Coagulation Pathways, StatPearls Publishing. Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK482253\/."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"515","DOI":"10.4103\/0019-5049.144643","article-title":"Overview of the coagulation system","volume":"58","author":"Palta","year":"2014","journal-title":"Indian J. Anaesth."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"367284","DOI":"10.4061\/2011\/367284","article-title":"Tissue Factor, Blood Coagulation, and Beyond: An Overview","volume":"2011","author":"Chu","year":"2011","journal-title":"Int. J. Inflamm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1160\/TH12-10-0772","article-title":"General mechanisms of coagulation and targets of anticoagulants (Section I)","volume":"109","author":"Husted","year":"2013","journal-title":"Thromb. Haemost."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1093\/eurheartj\/ehl492","article-title":"Anticoagulants in heart disease: Current status and perspectives","volume":"28","author":"Husted","year":"2007","journal-title":"Eur. Heart J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1160\/TH07-04-0274","article-title":"Update on antithrombin I (fibrin)","volume":"98","author":"Mosesson","year":"2007","journal-title":"Thromb. Haemost."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1093\/eurheartj\/ehp504","article-title":"Platelet thrombin receptor antagonism and atherothrombosis","volume":"31","author":"Angiolillo","year":"2009","journal-title":"Eur. Heart J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1056\/NEJMoa1200933","article-title":"Vorapaxar in the Secondary Prevention of Atherothrombotic Events","volume":"366","author":"Morrow","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"567","DOI":"10.14219\/jada.archive.2009.0227","article-title":"An Updated Concept of Coagulation with Clinical Implications","volume":"140","author":"Romney","year":"2009","journal-title":"J. Am. Dent. Assoc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1177\/0003319717739720","article-title":"Raised Fibrinogen Levels and Outcome in Outpatients with Peripheral Artery Disease","volume":"69","author":"Altes","year":"2018","journal-title":"Angiology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1161\/ATVBAHA.120.314774","article-title":"Plasma Biomarkers to Predict Cardiovascular Outcome in Patients with Peripheral Artery Disease","volume":"40","author":"Kremers","year":"2020","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s11239-019-01991-x","article-title":"Congenital hypofibrinogenemia associated with a novel heterozygous nonsense mutation in the globular C-terminal domain of the \u03b3-chain (p.Glu275Stop)","volume":"50","author":"Simurda","year":"2020","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Simurda, T., Brunclikova, M., Asselta, R., Caccia, S., Zolkova, J., Kolkova, Z., Loderer, D., Skornova, I., Hudecek, J., and Lasabova, Z. (2020). Genetic Variants in the FGB and FGG Genes Mapping in the Beta and Gamma Nodules of the Fibrinogen Molecule in Congenital Quantitative Fibrinogen Disorders Associated with a Thrombotic Phenotype. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134616"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s10555-017-9677-x","article-title":"Normal platelet function","volume":"36","author":"Holinstat","year":"2017","journal-title":"Cancer Metastasis Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1055\/s-0038-1675144","article-title":"Platelet Signaling in Primary Haemostasis and Arterial Thrombus Formation: Part I","volume":"38","author":"Scharf","year":"2018","journal-title":"Hamostaseologie"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.autrev.2010.07.016","article-title":"From endothelial dysfunction to atherosclerosis","volume":"9","author":"Sitia","year":"2010","journal-title":"Autoimmun. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s00441-008-0678-5","article-title":"Vascular endothelium in atherosclerosis","volume":"335","author":"Sima","year":"2009","journal-title":"Cell Tissue Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Simurda, T., Vilar, R., Zolkova, J., Ceznerova, E., Kolkova, Z., Loderer, D., Neerman-Arbez, M., Casini, A., Brunclikova, M., and Skornova, I. (2020). A Novel Nonsense Mutation in FGB (c.1421G>A; p.Trp474Ter) in the Beta Chain of Fibrinogen Causing Hypofibrinogenemia with Bleeding Phenotype. Biomedicines, 8.","DOI":"10.3390\/biomedicines8120605"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.avsg.2014.07.033","article-title":"Aging, Hypercoagulability, and Leg Necrosis in Critical Limb Ischemia","volume":"29","author":"Park","year":"2015","journal-title":"Ann. Vasc. Surg."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Saenz-Pipaon, G., Martinez-Aguilar, E., Orbe, J., Miqueo, A.G., Fernandez-Alonso, L., Paramo, J., and Roncal, C. (2021). The Role of Circulating Biomarkers in Peripheral Arterial Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073601"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Kietsiriroje, N., Ari\u00ebns, R.A., and Ajjan, R.A. (2021). Fibrinolysis in Acute and Chronic Cardiovascular Disease. Semin. Thromb. Hemost.","DOI":"10.1055\/s-0040-1718923"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1152\/japplphysiol.00885.2013","article-title":"Physiology in Medicine: Peripheral arterial disease","volume":"115","author":"Muller","year":"2013","journal-title":"J. Appl. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1161\/CIRCRESAHA.116.303566","article-title":"Pathogenesis of the Limb Manifestations and Exercise Limitations in Peripheral Artery Disease","volume":"116","author":"Hiatt","year":"2015","journal-title":"Circ. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e041715","DOI":"10.1136\/bmjopen-2020-041715","article-title":"Platelet aggregation inhibitor prescription for newly diagnosed peripheral arterial disease in the Netherlands: A cohort study","volume":"11","author":"Brand","year":"2021","journal-title":"BMJ Open"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1161\/CIRCULATIONAHA.120.047994","article-title":"Temporal Changes in Secondary Prevention and Cardiovascular Outcomes After Revascularization for Peripheral Arterial Disease in Denmark","volume":"143","author":"Nielsen","year":"2021","journal-title":"Circulation"},{"key":"ref_53","unstructured":"Warfarin Antiplatelet Vascular Evaluation Trial Investigators, Anand, S.S., Yusuf, S., Xie, C., Pogue, J., Eikelboom, J., Budaj, A., Sussex, B., Liu, L., and Guzman, R. (2007). Oral Anticoagulant and Antiplatelet Therapy and Peripheral Arterial Disease. N. Engl. J. Med., 357, 217\u2013227."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1055\/s-0038-1636530","article-title":"Rivaroxaban: A New Treatment Paradigm in the Setting of Vascular Protection?","volume":"118","author":"Zannad","year":"2018","journal-title":"Thromb. Haemost."},{"key":"ref_55","unstructured":"Cate, H.T., Guzik, T.J., Eikelboom, J., and Spronk, H.M.H. (2020). Pleiotropic actions of factor Xa inhibition in cardiovascular prevention: Mechanistic insights and implications for anti-thrombotic treatment. Cardiovasc. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa1112277","article-title":"Rivaroxaban in Patients with a Recent Acute Coronary Syndrome","volume":"366","author":"Mega","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1016\/S0140-6736(17)30751-1","article-title":"Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): A double-blind, multicentre, randomised trial","volume":"389","author":"Ohman","year":"2017","journal-title":"Lancet"},{"key":"ref_58","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":"ref_59","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":"ref_60","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","volume":"71","author":"Anand","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Kaplovitch, E., Eikelboom, J.W., Dyal, L., Aboyans, V., Abola, M.T., Verhamme, P., Avezum, A., Fox, K.A.A., Berkowitz, S.D., and Bangdiwala, S.I. (2020). Rivaroxaban and Aspirin in Patients With Symptomatic Lower Extremity Peripheral Artery Disease. JAMA Cardiol.","DOI":"10.1001\/jamacardio.2020.4390"},{"key":"ref_62","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":"ref_63","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":"ref_64","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1093\/eurheartj\/ehx658","article-title":"External applicability of the COMPASS trial: An analysis of the reduction of atherothrombosis for continued health (REACH) registry","volume":"39","author":"Darmon","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_65","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."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1177\/1526602818760488","article-title":"Edoxaban Plus Aspirin vs Dual Antiplatelet Therapy in Endovascular Treatment of Patients With Peripheral Artery Disease: Results of the ePAD Trial","volume":"25","author":"Moll","year":"2018","journal-title":"J. Endovasc. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1016\/S0140-6736(18)30832-8","article-title":"Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): An international, randomised, placebo-controlled trial","volume":"391","author":"Devereaux","year":"2018","journal-title":"Lancet"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.ahj.2020.06.010","article-title":"Rationale and design for the study Apixaban versus ClopidoGRel on a background of aspirin in patient undergoing InfraPoPliteal angioplasty for critical limb ischemia: AGRIPPA trial","volume":"227","author":"Biagioni","year":"2020","journal-title":"Am. Heart J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41573-020-0061-0","article-title":"Therapeutic strategies for thrombosis: New targets and approaches","volume":"19","author":"Mackman","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1160\/TH16-10-0807","article-title":"New developments in anticoagulants: Past, present and future","volume":"117","author":"Weitz","year":"2017","journal-title":"Thromb. Haemost."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/jth.15126","article-title":"New anticoagulants: Moving beyond the direct oral anticoagulants","volume":"19","author":"Fredenburgh","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3172","DOI":"10.1111\/jth.15093","article-title":"Factor XI, much more than an innocent observer","volume":"18","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1016\/j.jacc.2019.08.1028","article-title":"Anticoagulation With an Inhibitor of Factors XIa and XIIa During Cardiopulmonary Bypass","volume":"74","author":"Pireaux","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_74","unstructured":"Bristol-Myers-Squibb (2021, March 01). A Study on BMS-986177 for the Prevention of a Stroke in Patients Receiving Aspirin and Clopidogrel (AXIOMATIC-SSP) (NCT03766581), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/study\/NCT03766581."},{"key":"ref_75","unstructured":"Bayer (2021, March 01). Study to Gather Information about the Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following an Acute Heart Attack (PACIFIC-AMI) (NCT04304534), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04304534."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/13\/7113\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:24:36Z","timestamp":1760163876000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/13\/7113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,1]]},"references-count":75,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["ijms22137113"],"URL":"https:\/\/doi.org\/10.3390\/ijms22137113","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,1]]}}}