{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:06:40Z","timestamp":1760782000878,"version":"3.37.3"},"reference-count":17,"publisher":"Georg Thieme Verlag KG","issue":"07","license":[{"start":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T00:00:00Z","timestamp":1700697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Gates Philanthropy Partnerships and the Bill and Melinda Gates Foundation"},{"DOI":"10.13039\/100008897","name":"Janssen Pharmaceuticals","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008897","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:p>\n            Background\u2003We conducted a prespecified meta-analysis of two randomized, placebo-controlled trials of rivaroxaban 10\u2009mg daily in prehospital patients with acute coronavirus disease 2019 (COVID-19). Individually, the trials had limited power to detect a treatment effect due to recruitment stopping ahead of plan.<\/jats:p><jats:p>\n            Material and Methods\u2003The statistical analysis plan for the meta-analysis was finalized before unblinding of PREVENT-HD, the larger of the two trials. Pooled risk ratios and pooled risk differences along with the two-sided 95% confidence intervals were calculated using random-effect models.<\/jats:p><jats:p>\n            Results\u2003Rivaroxaban did not reduce the occurrence of either the primary prespecified endpoint, a composite of symptomatic arterial and venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, all-cause hospitalization, and all-cause mortality (risk difference: 0.0044; 95% confidence interval: \u22120.0263, 0.0175; p\u2009=\u20090.69 for pooled risk difference) or the secondary endpoint of all-cause hospitalization (p\u2009=\u20090.76). Although thrombotic events were infrequent, pooled analysis did reveal that rivaroxaban reduced arterial and venous thrombotic events (placebo 6 events, rivaroxaban 0 events; pooled risk difference: \u22120.0068; 95% confidence interval: \u22120.0132, \u22120.0006; p\u2009=\u20090.03). In the pooled studies, only one major bleeding event was observed in a rivaroxaban-allocated patient with no critical site or fatal bleeding events.<\/jats:p><jats:p>\n            Conclusion\u2003Although this meta-analysis does not support antithrombotic prophylaxis with rivaroxaban in a broad prehospital population with acute COVID-19, the prevention of arterial and venous thrombotic events among rivaroxaban-allocated patients is consistent with the known thromboprophylactic effect of the drug in medically ill patients.<\/jats:p>","DOI":"10.1055\/a-2216-5848","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T23:54:56Z","timestamp":1700783696000},"page":"649-655","source":"Crossref","is-referenced-by-count":1,"title":["Antithrombotic Prophylaxis with Rivaroxaban in Patients with Prehospital COVID-19: A Meta-analysis of Two Placebo-Controlled Trials"],"prefix":"10.1055","volume":"124","clinical-trial-number":[{"clinical-trial-number":"nct04508023","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04504032","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3413-7836","authenticated-orcid":false,"given":"Judith","family":"Hsia","sequence":"additional","affiliation":[{"name":"Colorado Prevention Center and Department of Medicine, University of Colorado, Aurora, Colorado, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3175-461X","authenticated-orcid":false,"given":"Alex C.","family":"Spyropoulos","sequence":"additional","affiliation":[{"name":"Feinstein Institutes for Medical Research and Department of Medicine, Northwell Health, New York, New York, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Piazza","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Weng","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Statistical Decision Sciences, Cardiovascular and Metabolism, High Wycombe, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael W.","family":"Dunne","sequence":"additional","affiliation":[{"name":"Bill and Melinda Gates Medical Research Institute, Cambridge, Massachusetts, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Concetta","family":"Lipardi","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Clinical Development, Raritan, New Jersey, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7744-1486","authenticated-orcid":false,"given":"Elliot S.","family":"Barnathan","sequence":"additional","affiliation":[{"name":"Janssen Research and Development, Clinical Development, Raritan, New Jersey, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc P.","family":"Bonaca","sequence":"additional","affiliation":[{"name":"Colorado Prevention Center and Department of Medicine, University of Colorado, Aurora, Colorado, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"issue":"08","key":"ref3","doi-asserted-by":"crossref","first-page":"e594","DOI":"10.1016\/S2352-3026(22)00173-9","article-title":"Thromboprophylactic low-molecular-weight heparin versus standard of care in unvaccinated, at-risk outpatients with COVID-19 (ETHIC): an open-label, multicentre, randomised, controlled, phase 3b trial","volume":"9","author":"F Cools","year":"2022","journal-title":"Lancet Haematol"},{"issue":"08","key":"ref4","doi-asserted-by":"crossref","first-page":"e585","DOI":"10.1016\/S2352-3026(22)00175-2","article-title":"Enoxaparin for primary thromboprophylaxis in symptomatic outpatients with COVID-19 (OVID): a randomised, open-label, parallel-group, multicentre, phase 3 trial","volume":"9","author":"S Barco","year":"2022","journal-title":"Lancet Haematol"},{"issue":"17","key":"ref5","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1001\/jama.2021.17272","article-title":"Effect of antithrombotic therapy on clinical outcomes in outpatients with clinically stable symptomatic COVID-19: the ACTIV-4B randomized clinical trial","volume":"326","author":"J M Connors","year":"2021","journal-title":"JAMA"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"102004","DOI":"10.1016\/j.eclinm.2023.102004","article-title":"Rivaroxaban to prevent major clinical outcomes in non-hospitalised patients with COVID-19: the CARE - COALITION VIII randomised clinical trial","volume":"60","author":"\u00c1 Avezum","year":"2023","journal-title":"EClinicalMedicine"},{"issue":"01","key":"ref8","doi-asserted-by":"crossref","first-page":"e473","DOI":"10.1093\/cid\/ciab813","article-title":"Randomized study of rivaroxaban vs placebo on disease progression and symptoms resolution in high-risk adults with mild coronavirus disease 2019","volume":"75","author":"J Ananworanich","year":"2022","journal-title":"Clin Infect Dis"},{"issue":"25","key":"ref9","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1161\/CIRCULATIONAHA.123.063901","article-title":"Rivaroxaban for prevention of thrombotic events, hospitalization, and death in outpatients with COVID-19: a randomized clinical trial","volume":"147","author":"G Piazza","year":"2023","journal-title":"Circulation"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.jvsv.2020.12.012","article-title":"Suldexide in the treatment of early stages of COVID-19","volume":"9","author":"A Gonzalez-Ochoa","year":"2021","journal-title":"J Vasc Surg Venous Lymphat Disord"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ahj.2021.02.001","article-title":"Rationale and design for the study of rivaroxaban to reduce the risk of major venous and arterial thrombotic events, hospitalization and death in medically ill outpatients with symptomatic COVID-19: the PREVENT-HD study","volume":"235","author":"W Capell","year":"2021","journal-title":"Am Heart J"},{"issue":"12","key":"ref12","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1056\/NEJMoa1805090","article-title":"Rivaroxaban for thromboprophylaxis after hospitalization for medical illness","volume":"379","author":"A C Spyropoulos","year":"2018","journal-title":"N Engl J Med"},{"issue":"04","key":"ref13","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1111\/j.1538-7836.2005.01204.x","article-title":"Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients","volume":"3","author":"S Schulman","year":"2005","journal-title":"J Thromb Haemost"},{"issue":"03","key":"ref14","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":"R DerSimonian","year":"1986","journal-title":"Control Clin Trials"},{"issue":"04","key":"ref15","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1161\/CIRCRESAHA.120.317447","article-title":"The emerging threat of (micro)thrombosis in COVID-10 and its therapeutic implications","volume":"127","author":"J D McFadyen","year":"2020","journal-title":"Circ Res"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/S0140-6736(21)01906-1","article-title":"Studying the coagulopathy of COVID-19","volume":"399","author":"A C Spyropoulos","year":"2022","journal-title":"Lancet"},{"issue":"21","key":"ref17","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1056\/NEJMoa2000052","article-title":"Rivaroxaban in peripheral artery disease after revascularization","volume":"382","author":"M P Bonaca","year":"2020","journal-title":"N Engl J Med"},{"issue":"18","key":"ref18","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1016\/j.jacc.2020.08.070","article-title":"Registry of arterial and venous thromboembolic complications in patients with COVID-19","volume":"76","author":"G Piazza","year":"2020","journal-title":"J Am Coll Cardiol"},{"volume-title":"Coronavirus Disease 2019 (COVID-19) treatment guidelines","author":"COVID-19 Treatment Guidelines Panel","key":"ref19"},{"issue":"35","key":"ref20","doi-asserted-by":"crossref","first-page":"e2105482118","DOI":"10.1073\/pnas.2105482118","article-title":"Intensity and frequency of extreme novel epidemics","volume":"118","author":"M Marani","year":"2021","journal-title":"Proc Natl Acad Sci U S A"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2216-5848.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T10:18:59Z","timestamp":1730801939000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2216-5848"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,23]]},"references-count":17,"journal-issue":{"issue":"07","published-online":{"date-parts":[[2024,6,25]]},"published-print":{"date-parts":[[2024,7]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2216-5848","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"type":"print","value":"0340-6245"},{"type":"electronic","value":"2567-689X"}],"subject":[],"published-other":{"date-parts":[[2023,11,23]]},"published":{"date-parts":[[2023,11,23]]}}}