{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:04:13Z","timestamp":1790179453078,"version":"4.1.0"},"reference-count":18,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Coagulopathy in the context of COVID-19 is a major threat due to deep vein thromboses and pulmonary embolisms.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To assess whether therapeutic anticoagulation on top of standard of care (SOC) compared with prophylactic anticoagulation as part of SOC can improve objective patient-relevant end points.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This prospective, assessor-blinded, multicenter, parallel-group (1:1), placebo-controlled, superiority randomized clinical trial (HERO-19) assessed patients with a confirmed diagnosis of COVID-19 who were hospitalized in an intensive care unit or non\u2013intensive care ward at 1 of 10 university hospitals in Germany from November 12, 2020, to January 15, 2023. Data analysis was conducted after the final database lock in February 2024.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Patients were treated for 42 days. Patients enrolled in the experimental group received therapeutic anticoagulation using low-molecular-weight heparin (LMWH) body weight adapted during the hospital stay and oral anticoagulation using edoxaban, 60 mg daily, after being discharged from the hospital. Patients enrolled in the control group received prophylactic anticoagulation using LMWH as part of SOC while in the hospital and placebo after discharge.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary end point was time to the first occurrence of all-cause mortality and\/or venous thromboembolism and\/or arterial thromboembolism within up to 42 days. Potential thromboembolic events were assessed by duplex ultrasonography of arms and legs at day 14 or discharge and day 42. The primary safety outcome was major and clinically relevant nonmajor bleeding according to International Society on Thrombosis and Haemostasis classification.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 139 patients (mean [SD] age, 58.4\u2009[13.7] years; 93 [67%] male and 46 [33%] female) were included in the study. Of these, 71 patients (51%) were randomized to prophylactic anticoagulation group, whereas 68 (49%) were randomized to the therapeutic anticoagulation group. The primary outcome occurred in 14 of 67 patients (21%; 2.31 incidence per patient-year) assigned to therapeutic anticoagulation and 20 of 70 (29%; 3.37 incidence per patient-year) assigned to prophylactic anticoagulation (primary end point assessment not available for 2 patients) with primary end point assessment (hazard ratio, 0.74; 95% CI, 0.38-1.48;\n P<\/jats:italic>\n \u2009=\u2009.40). In the per-protocol analysis, the hazard ratio was 0.66 (95% CI, 0.32-1.37;\n P<\/jats:italic>\n \u2009=\u2009.26). A total of 7 bleeding events occurred in the intervention group, whereas 6 bleeding events occurred in the control group.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In patients hospitalized with COVID-19, in-hospital therapeutic anticoagulation with LMWH followed by edoxaban to day 42 did not statistically significantly reduce death and\/or thromboembolic events compared with prophylactic anticoagulation followed by placebo.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT04542408<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.35333","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:30:27Z","timestamp":1790177427000},"page":"e2635333","source":"Crossref","is-referenced-by-count":0,"title":["Prophylactic vs Therapeutic Anticoagulation in Hospitalized Patients With COVID-19"],"prefix":"10.1001","volume":"9","author":[{"given":"Mahir","family":"Karakas","sequence":"first","affiliation":[{"name":"Department of Intensive Care Medicine, University Medical Center Hamburg, Hamburg, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), Hamburg-Kiel-L\u00fcbeck Partner Site, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva Sophia","family":"Nicolay","sequence":"additional","affiliation":[{"name":"Department of Medicine 3, University Medical Center Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Wichmann","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, University Medical Center Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Schmiedel","sequence":"additional","affiliation":[{"name":"Department of Medicine 1, University Medical Center Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marylyn M.","family":"Addo","sequence":"additional","affiliation":[{"name":"Department of Medicine 1, University Medical Center Hamburg, Hamburg, Germany"},{"name":"German Center for Infection Research (DZIF), Hamburg-L\u00fcbeck-Borstel-Riems Partner Site, Hamburg, Germany"},{"name":"Institute for Infection Research and Vaccine Development, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Nosko","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, University Medical Center Hamburg, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Lund","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, University Medical Center Hamburg, Hamburg, 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