COVID-19 Anticoagulation Regimen Misses HERO-19 Primary Endpoint

Therapeutic anticoagulation during hospitalization followed by edoxaban after discharge did not significantly reduce death or thromboembolic events compared with prophylactic anticoagulation followed by placebo in patients hospitalized with COVID-19. The findings from the HERO-19 randomized clinical trial were published in JAMA Network Open.

The assessor-blinded trial analyzed 139 patients at 10 university hospitals in Germany between November 2020 and January 2023. Participants included patients in intensive care units and other hospital wards. Patients and treating clinicians knew the treatment assignment, while outcome assessors were blinded. Investigators assigned 68 patients to therapeutic anticoagulation and 71 to prophylactic anticoagulation.

The therapeutic group received full-dose low-molecular-weight heparin or fondaparinux in the hospital, followed by edoxaban after discharge through day 42. The comparison group received prophylactic-dose anticoagulation during hospitalization and placebo after discharge. The primary outcome was time to the first occurrence of death, venous thromboembolism, or arterial thromboembolism within 42 days; investigators also used serial duplex ultrasonography to identify thromboembolic events.

The primary outcome occurred in 14 of 67 evaluable patients (21%) in the therapeutic group and 20 of 70 (29%) in the prophylactic group (hazard ratio, 0.74; 95% CI, 0.38-1.48; P = .40). Primary outcome data were unavailable for two patients. Seven deaths occurred in the therapeutic group and eight in the prophylactic group. Investigators reported seven major or clinically relevant nonmajor bleeding events with therapeutic anticoagulation versus four with prophylactic anticoagulation.

Enrollment ended below the recalculated sample size because of recruitment difficulties, and the authors noted that the trial may have lacked power to detect a smaller treatment effect. They concluded that the findings do not support routine escalation from prophylactic to therapeutic anticoagulation for this outcome in the studied population.

Source: 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