Full-dosing of anticoagulation does little to improve outcomes in patients hospitalized with COVID-19 when compared with prophylactic dosing, as shown in the HERO-19 trial.
During the 42-day follow-up, the primary endpoint of a composite of all-cause mortality, venous thromboembolism, or arterial thromboembolism occurred in 21 percent of patients who received therapeutic anticoagulation with low-molecular-weight heparin (LMWH) followed by edoxaban vs 29 percent of those who received prophylactic anticoagulation with LMWH followed by placebo, corresponding to rates of 2.31 and 3.37 incidence per patient-year, respectively. [JAMA Netw Open 2026;9:e2635333]
“Therapeutic dosing did not statistically significantly reduce time to a composite of death and/or arterial and/or venous thromboembolic events compared with prophylactic anticoagulation (hazard ratio [HR], 0.74, 95 percent confidence interval [CI], 0.38–1.48; p=0.40),” the investigators said.
Subgroup analyses yielded consistent results across individuals in the ICU vs those in the non-ICU ward and in males vs females.
In terms of safety, serious adverse events occurred with less frequency in the therapeutic vs prophylactic dose group (39.6 percent vs 60.4 percent). There were no suspected unexpected, serious adverse reactions reported, nor were there any study drug–related deaths or new treatment-emergent adverse events. Seven bleeding events occurred in the therapeutic dose group and six in the prophylactic dose group.
Overall, mortality in hospitalized patients with COVID-19 reached 11 percent during the 42-day follow-up, with a 10-percent arterial event rate and a 6-percent venous thromboembolic event rate.
“HERO-19 represents the first anticoagulation study, to our knowledge, to apply thorough clinical follow-up with serial duplex ultrasonography of the arms and legs,” they said. “Consequently, an important and new finding of our study is that most contemporary anticoagulation trials seem to have underestimated the rates of thromboembolic events because they only assessed clinically apparent events.”
The findings do not support routine escalation from prophylactic to therapeutic anticoagulation, according to the investigators. However, systematic vascular surveillance revealed a substantial thromboembolic burden and underscores the need to identify patients who may benefit from intensified or extended anticoagulation, they added.
The investigators also acknowledged the possibility that prolonged, low-intensity anticoagulation after discharge may be more effective and safer than intensive full-dose regimens during the short-term phase, in line with recent data supporting extended thromboprophylaxis in high-risk medical patients.
“Additional studies specifically addressing the optimal dose and duration of post-discharge anticoagulation in COVID-19 are warranted,” they added.
HERO-19 included 139 patients (mean age 58.4 years, 67 percent male) hospitalized with COVID-19. These patients were randomly allocated to either the therapeutic anticoagulation group (n=68) or the prophylactic anticoagulation group (n=71). Patients in the therapeutic dose group received LMWH adapted to body weight during the hospital stay and oral anticoagulation with edoxaban at 60 mg daily after being discharged. Those in the prophylactic dose group received LMWH and fondaparinux in a prophylactic dose during the hospital stay and oral placebo after discharge until day 42.
Numerically fewer rehospitalizations within 42 days occurred in the therapeutic vs the prophylactic anticoagulation group (1 vs 6 events; odds ratio, 0.16, 95 percent CI, 0.02–1.37; p=0.09). A total of 25 patients in each group received mechanical ventilatory support, and the mean duration of ventilatory support was 249.7 h in the therapeutic anticoagulation group vs 281.1 h in the prophylactic anticoagulation group. Mean duration of kidney replacement therapy was 14 vs 20.8 days, respectively.