Therapeutic Anticoagulation Shows No Significant Benefit in Hospitalized COVID-19 Patients: JAMA
Germany: A new study published in JAMA Network Open has revealed that among hospitalized patients with COVID-19, therapeutic anticoagulation with LMWH followed by edoxaban through day 42 did not significantly reduce death or thromboembolic events compared with prophylactic anticoagulation followed by placebo. The findings do not support routine therapeutic anticoagulation for this purpose.
The findings are from the HERO-19 randomized clinical trial, led by Mahir Karakas, Department of Intensive Care Medicine, University Medical Center Hamburg, Hamburg, Germany, and colleagues.
COVID-19 can be accompanied by coagulation abnormalities and an increased risk of venous and arterial thromboembolic complications, including deep vein thrombosis and pulmonary embolism. The trial evaluated whether using full-dose anticoagulation instead of standard prophylactic dosing could improve clinically important outcomes among hospitalized patients.
The prospective, assessor-blinded, multicenter trial was conducted across 10 university hospitals in Germany between November 2020 and January 2023. It included adults with confirmed COVID-19 who were hospitalized in intensive care or non-intensive care wards.
A total of 139 patients were included, with a mean age of 58.4 years; 93 (67%) were men and 46 (33%) were women. Participants were randomly assigned to therapeutic or prophylactic anticoagulation.
Patients in the therapeutic group received weight-adjusted LMWH during hospitalization, followed by 60 mg of oral edoxaban daily after discharge through day 42. The control group received prophylactic LMWH during hospitalization and placebo after discharge.
The primary outcome was the time to the first occurrence of all-cause death, venous thromboembolism, or arterial thromboembolism within 42 days. Bleeding classified according to International Society on Thrombosis and Haemostasis criteria was assessed as the primary safety outcome.
Key findings:
- The primary outcome occurred in 14 of 67 patients (21%) receiving therapeutic anticoagulation compared with 20 of 70 (29%) receiving prophylactic anticoagulation.
- The hazard ratio was 0.74, indicating that the difference was not statistically significant.
- In the per-protocol analysis, the hazard ratio was 0.66.
- Seven bleeding events occurred in the therapeutic anticoagulation group compared with six in the prophylactic group.
- Systematic duplex ultrasonography identified a substantial thromboembolic burden despite anticoagulation strategies.
The researchers noted several limitations. Early-pandemic assumptions may have overestimated event rates, potentially leaving the study underpowered to detect smaller treatment effects. The open-label design may have introduced bias, although outcome assessors were blinded. Limited baseline data and the composite endpoint also restricted interpretation and generalizability. Additionally, patients with prolonged hospitalization had limited exposure to edoxaban because it was started only after discharge.
Overall, therapeutic LMWH followed by edoxaban was well tolerated but did not significantly reduce death or thromboembolic events compared with prophylactic anticoagulation. The findings do not support routine escalation to therapeutic anticoagulation in hospitalized patients with COVID-19.
Reference:
Karakas M, Nicolay SS, Wichmann D, et al. Prophylactic vs Therapeutic Anticoagulation in Hospitalized Patients With COVID-19: A Randomized Clinical Trial. JAMA Netw Open. 2026;9(9):e2635333. doi:10.1001/jamanetworkopen.2026.35333
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