{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T12:04:21Z","timestamp":1792757061427,"version":"4.5.0"},"reference-count":32,"publisher":"Georg Thieme Verlag KG","issue":"08","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Thrombotic cardiovascular disease (myocardial infarction [MI], stroke, and venous thromboembolism [VTE]) remains a major cause of death and disability. Sulodexide is an oral glycosaminoglycan containing heparan sulfate and dermatan sulfate. We conducted a systematic review and meta-analysis to determine the cardiovascular efficacy, and safety of sulodexide versus control in randomized controlled trials (RCTs). We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for RCTs reporting cardiovascular outcomes in patients receiving sulodexide versus control (placebo or no treatment). Outcomes included all-cause mortality, cardiovascular mortality, MI, stroke, deep vein thrombosis (DVT), pulmonary embolism, and bleeding. We used inverse variance random-effects models with odds ratio (OR) as the effect measure. After screening 360 records, 6 RCTs including 7,596 patients (median follow-up duration: 11.6 months) were included. Patients were enrolled for history of MI, VTE, peripheral arterial disease, or cardiovascular risk factors plus nephropathy. Use of sulodexide compared with control was associated with reduced odds of all-cause mortality (OR 0.67, 95% confidence interval [CI] 0.52\u20130.85, p\u2009=\u20090.001), cardiovascular mortality (OR 0.44, 95% CI 0.22\u20130.89, p\u2009=\u20090.02), and MI (OR 0.70, 95% CI 0.51\u20130.96, p\u2009=\u20090.03), and nonsignificantly reduced odds of stroke (OR 0.78, 95% CI 0.45\u20131.35, p\u2009=\u20090.38). Sulodexide was associated with significantly reduced odds of VTE (OR 0.44, 95% CI 0.24\u20130.81, p\u2009=\u20090.008), including DVT (OR 0.41, 95% CI 0.26\u20130.65, p\u2009&lt;\u20090.001), but not pulmonary embolism (OR 0.92, 95% CI 0.40\u20132.15, p\u2009=\u20090.86). Bleeding events were not significantly different in the two groups (OR 1.14, 95% CI 0.47\u20132.74, p\u2009=\u20090.48). In six RCTs across a variety of clinical indications, use of sulodexide compared with placebo or no treatment was associated with reduced odds of all-cause mortality, cardiovascular mortality, MI, and DVT, without a significant increase in bleeding. Additional studies with this agent are warranted.<\/jats:p>","DOI":"10.1055\/s-0040-1716874","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T19:16:25Z","timestamp":1603307785000},"page":"908-918","source":"Crossref","is-referenced-by-count":32,"title":["Sulodexide versus Control and the Risk of Thrombotic and Hemorrhagic Events: Meta-Analysis of Randomized Trials"],"prefix":"10.1055","volume":"46","author":[{"given":"Behnood","family":"Bikdeli","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Boston, Massachusetts"},{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Center for Outcomes Research and Evaluation (CORE), Yale University School of Medicine, New Haven, Connecticut"},{"name":"Clinical Trials Center, Cardiovascular Research Foundation, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurav","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Hoffman Heart Institute, Saint Francis Hospital, University of Connecticut, Hartford, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay J.","family":"Kirtane","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Boston, Massachusetts"},{"name":"Clinical Trials Center, Cardiovascular Research Foundation, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahil A.","family":"Parikh","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Boston, Massachusetts"},{"name":"Clinical Trials Center, Cardiovascular Research Foundation, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe M.","family":"Andreozzi","sequence":"additional","affiliation":[{"name":"Angiology Care Unit, University of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nihar R.","family":"Desai","sequence":"additional","affiliation":[{"name":"Center for Outcomes Research and Evaluation (CORE), Yale University School of Medicine, New Haven, Connecticut"},{"name":"Section of Cardiovascular Medicine, Yale School of Medicine, Yale University, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic P.","family":"Francese","sequence":"additional","affiliation":[{"name":"Clinical Trials Center, Cardiovascular Research Foundation, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C Michael","family":"Gibson","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Piazza","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Boston, Massachusetts"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel Z.","family":"Goldhaber","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Boston, Massachusetts"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Eikelboom","sequence":"additional","affiliation":[{"name":"Division of Hematology and Thromboembolism, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harlan M.","family":"Krumholz","sequence":"additional","affiliation":[{"name":"Center for Outcomes Research and Evaluation (CORE), Yale University School of Medicine, New Haven, Connecticut"},{"name":"Section of Cardiovascular Medicine, Yale School of Medicine, Yale University, New Haven, Connecticut"},{"name":"Department of Health Policy and Management, Yale School of Public Health, Yale University, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg W.","family":"Stone","sequence":"additional","affiliation":[{"name":"Clinical Trials Center, Cardiovascular Research Foundation, New York, New York"},{"name":"The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2020,10,21]]},"reference":[{"issue":"10","key":"ref1","doi-asserted-by":"crossref","first-page":"e146","DOI":"10.1161\/CIR.0000000000000485","article-title":"Heart Disease and Stroke Statistics-2017 Update: a report from the American Heart Association","volume":"135","author":"E J Benjamin","year":"2017","journal-title":"Circulation"},{"issue":"09","key":"ref2","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1161\/CIRCRESAHA.115.306841","article-title":"Global burden of thrombosis: epidemiologic aspects","volume":"118","author":"A M Wendelboe","year":"2016","journal-title":"Circ Res"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1056\/NEJMra1112570","article-title":"A tale of coronary artery disease and myocardial infarction","volume":"366","author":"E G Nabel","year":"2012","journal-title":"N Engl J Med"},{"issue":"06","key":"ref4","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1097\/MCA.0000000000000279","article-title":"Natural history of coronary atherosclerosis: did contemporary medical therapy change the course?","volume":"26","author":"D L Ain","year":"2015","journal-title":"Coron Artery Dis"},{"issue":"04","key":"ref5","doi-asserted-by":"crossref","first-page":"241","DOI":"10.7326\/0003-4819-143-4-200508160-00005","article-title":"Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: meta-analysis with estimates of risk and benefit","volume":"143","author":"M B Rothberg","year":"2005","journal-title":"Ann Intern Med"},{"issue":"08","key":"ref6","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJMoa1105819","article-title":"Apixaban with antiplatelet therapy after acute coronary syndrome","volume":"365","author":"J H Alexander","year":"2011","journal-title":"N Engl J Med"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0140-6736(09)60738-8","article-title":"Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial","volume":"374","author":"J L Mega","year":"2009","journal-title":"Lancet"},{"issue":"14","key":"ref8","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":"J W Eikelboom","year":"2017","journal-title":"N Engl J Med"},{"issue":"06","key":"ref9","first-page":"CD010694","article-title":"Sulodexide for treating venous leg ulcers","author":"B Wu","year":"2016","journal-title":"Cochrane Database Syst Rev"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2147\/DDDT.S6762","article-title":"Development and use of sulodexide in vascular diseases: implications for treatment","volume":"8","author":"S Coccheri","year":"2013","journal-title":"Drug Des Devel Ther"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"105","DOI":"10.2147\/JBM.S10558","article-title":"Use of sulodexide in patients with peripheral vascular disease","volume":"1","author":"J Lasierra-Cirujeda","year":"2010","journal-title":"J Blood Med"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/j.1527-3466.2006.00214.x","article-title":"Sulodexide: a renewed interest in this glycosaminoglycan","volume":"24","author":"D A Lauver","year":"2006","journal-title":"Cardiovasc Drug Rev"},{"issue":"02","key":"ref13","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1185\/03007999309111537","article-title":"Pharmacodynamic effects of single and repeated doses of oral sulodexide in healthy volunteers. 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