{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:57:58Z","timestamp":1760144278191,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T00:00:00Z","timestamp":1711843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Objectives: To review the evidence on the effectiveness and safety of low-dose-rivaroxaban 2.5 mg twice daily (LDR) in patients with coronary artery disease (CAD) and\/or peripheral artery disease (PAD) taking antiplatelets. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs). Efficacy endpoints were cardiovascular events (CVEs), myocardial infarction, stroke, all-cause, and cardiovascular death. Any, major, fatal bleeding, and intracranial hemorrhage (ICH) were safety endpoints. Numbers needed to treat (NNT), and numbers needed to harm (NNH) were also calculated. Results: Seven RCTs were included with 45,836 patients: 34,276 with CAD and 11,560 with PAD. Overall, 4247 CVEs and 3082 bleedings were registered. LDR in association with either any antiplatelet drug or aspirin (ASA) alone reduced the risk of CVEs (hazard ratio [HR] 0.86, 95% confidence interval [95%CI] 0.78\u20130.94) and ischemic stroke (HR 0.68, 95%CI 0.55\u20130.84). LDR + ASA increased the risk of major bleeding (HR 1.71, 95%CI 1.38\u20132.11) but no excess of fatal bleeding or ICH was found. The NNT to prevent one CVE for LDR + ASA was 63 (43\u2013103) and the NNH to cause major bleeding was 107 (77\u2013193). Conclusions: The combination of LDR with either antiplatelet drugs or low-dose aspirin reduces CVEs and ischemic stroke in patients with CAD\/PAD. There was an increased risk of major bleeding but no excess of fatal or ICH was found. LDR seems to have a favorable net clinical benefit compared to ASA treatment alone.<\/jats:p>","DOI":"10.3390\/jcm13072033","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T13:32:56Z","timestamp":1711891976000},"page":"2033","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Combination Therapy with Low-Dose Rivaroxaban in Patients with Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2895-6234","authenticated-orcid":false,"given":"Tommaso","family":"Bucci","sequence":"first","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool and Heart and Chest Hospital, Liverpool L7 8TX, UK"},{"name":"Department of General and Specialized Surgery, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7781-6636","authenticated-orcid":false,"given":"Francesco","family":"Del Sole","sequence":"additional","affiliation":[{"name":"Department of Clinical, Internal Medicine, Anaesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9467-5903","authenticated-orcid":false,"given":"Danilo","family":"Menichelli","sequence":"additional","affiliation":[{"name":"Department of General and Specialized Surgery, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5941-9947","authenticated-orcid":false,"given":"Gioacchino","family":"Galardo","sequence":"additional","affiliation":[{"name":"Department of General and Specialized Surgery, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavio Giuseppe","family":"Biccir\u00e8","sequence":"additional","affiliation":[{"name":"Department of General and Specialized Surgery, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessio","family":"Farcomeni","sequence":"additional","affiliation":[{"name":"Department of Economics and Finance, University of Rome \u201cTor Vergata,\u201d Via Columbia 2, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory Y. H.","family":"Lip","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool and Heart and Chest Hospital, Liverpool L7 8TX, UK"},{"name":"Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University, 9220 Aalborg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2265-7455","authenticated-orcid":false,"given":"Pasquale","family":"Pignatelli","sequence":"additional","affiliation":[{"name":"Department of Clinical, Internal Medicine, Anaesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6357-5213","authenticated-orcid":false,"given":"Daniele","family":"Pastori","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool and Heart and Chest Hospital, Liverpool L7 8TX, UK"},{"name":"Department of Clinical, Internal Medicine, Anaesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1177\/0003319707302494","article-title":"The prevalence of peripheral arterial disease in high risk subjects and coronary or cerebrovascular patients","volume":"58","author":"Poredos","year":"2007","journal-title":"Angiology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1001\/jama.286.11.1317","article-title":"Peripheral arterial disease detection, awareness, and treatment in primary care","volume":"286","author":"Hirsch","year":"2001","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e185239","DOI":"10.1001\/jamanetworkopen.2018.5239","article-title":"Polyvascular Disease and Risk of Major Adverse Cardiovascular Events in Peripheral Artery Disease: A Secondary Analysis of the EUCLID Trial","volume":"1","author":"Gutierrez","year":"2018","journal-title":"JAMA Netw. 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