Extending Anticoagulation is Reasonable in Children with VTE, Data Suggest

Extended anticoagulation in children has been correlated with low incidences of recurrent venous thromboembolism (VTE) and bleeding during extended-phase anticoagulant treatment in the phase III EINSTEIN Jr trial. The findings demonstrated similarity to those of patients observed during acute-phase treatment and adult clinical trials, representing important clinical considerations for the use of extended anticoagulation.¹

Spanning 28 countries, the EINSTEIN-Jr trial was launched to compare rivaroxaban with standard anticoagulation in 500 pediatric patients with VTE. A team of international experts subsequently conducted a cohort study to evaluate extended-phase anticoagulant therapy in a set of patients from this trial, as well as identify factors that drive the clinical decision to extend anticoagulation.¹

Regarding rivaroxaban specifically, cohort study first author Christoph Male, MD, MSc, of the Medical University of Vienna, Austria, noted in remarks forwarded to Heme Today that the EINSTEIN Jr studies “established bodyweight-adjusted doses for all pediatric age groups and an age-appropriate oral administration formulation for flexible use in young children, now available for clinical practice.”

The cohort study included 248 patients aged 17 years and younger, all of whom underwent 3 months of anticoagulation for acute VTE, or 1 month for patients younger than 2 years with catheter-related VTE. Following this acute-phase treatment, patients received extended-phase anticoagulation for up to 9 months or up to 2 months for those younger than 2 years with catheter-related VTE. The study anticoagulants that patients received during this extended phase were bodyweight-adjusted rivaroxaban, administered as tablets or in-suspension as 20 mg equivalent doses, or standard anticoagulation with heparin or a vitamin K antagonist. 214 patients received their extended-phase anticoagulation within the framework of the study while 34 received it outside that framework.¹

Among the patients who had received extended-phase anticoagulation within the framework of the study, 1% had recurrent VTE over the course of that treatment, with a cumulative incidence of 3%. Two percent of patients who received extended-phase anticoagulation within the study framework experienced clinically relevant non-major bleeding, with a cumulative incidence of 3.3%. There was no major bleeding or fatal VTEs.¹

Dr. Male highlighted about the results of the extended-phase anticoagulation that “incidences of recurrent VTE and relevant bleeding were low and similar to those observed during the preceding acute treatment phase and adult studies on extended-phase anticoagulant treatment.”

Key factors identified by the investigators as associated with the clinical decision to extend anticoagulation were symptomatic index VTE, unprovoked VTE or persistent risk factor, and residual thrombosis on repeat imaging, with odds ratios of 1.88, 2.16, and 3.79, respectively. They also found that rivaroxaban and standard anticoagulation had similar outcome rates.¹

“Based on the similar clinical course of VTE and outcomes for children and adults, the overall evidence from the EINSTEIN trials provide valuable reassurance for the efficacious and safe use of rivaroxaban for both acute- and extended-phase anticoagulation of VTE in children of all ages,” Dr. Male explained.

In additional comments forwarded to Heme Today, study coauthor Paul Monagle, MBBS, MD, MSc, of the University of Melbourne, Australia, elaborated on the meaning of the trial results for rivaroxaban in pediatric VTE management. Namely, “[g]iven the reduced burden of care compared to previous options (subcutaneous low-molecular-weight heparin or warfarin requiring regular monitoring) extended phase rivaroxaban (oral medication and no monitoring required) will improve quality of life for many children requiring extended phase therapy with no loss of efficacy or safety.”

Reference

1. Male C, Lensing AWA, Chan AKC, et al. Extended-phase anticoagulant treatment of acute venous thromboembolism in children: a cohort study from the EINSTEIN-Jr phase 3 trial. Lancet Haematol. 2025;12(5):e357-e364. doi:10.1016/S2352-3026(25)00067-5

EINSTEIN-Jr and the cohort study were funded by Bayer and Janssen Research & Development.