The direct oral anticoagulant (DOAC) dabigatran demonstrated non-inferiority to standard of care in children with thrombophilia, indicating that it could be an appropriate long-term anticoagulant, according to a study in Blood Advances.
The role of thrombophilia is controversial in pediatric thrombosis, according to study author Leonardo R. Brandão, MD, of the Hospital for Sick Children in Toronto. There is currently no preferred anticoagulation agent recommended for long-term use in pediatric subgroups like thrombophilia.
“Increasingly, its importance has been more widely accepted, particularly in patients with unprovoked venous thrombotic events, in whom thrombophilia seems to be associated with recurrences,” Dr. Brandão said. “Commonly, patients with thrombophilia are anticoagulated for at least six to 12 months. Therefore, having access to an oral anticoagulant agent such as dabigatran etexilate that does not require laboratory monitoring and has similar efficacy to standard-of-care anticoagulation is highly relevant in this scenario.”
To investigate the efficacy and safety of dabigatran in children with thrombophilia compared to those without, Dr. Brandão and colleagues combined data from two large, international trials looking at acute venous thromboembolism (VTE) in children. The phase IIb/III DIVERSITY trial showed three months’ treatment with dabigatran was non-inferior to standard of care for acute VTE in children. A single-arm, phase III secondary VTE prevention study showed that up to 12 months of dabigatran therapy had a favorable safety profile.
Dr. Brandão and colleagues assessed the data for the primary composite efficacy endpoint of complete thrombus resolution and freedom from VTE recurrence or VTE-related death.
In the DIVERSITY trial, 36% of patients in the thrombophilia subgroup who were treated with dabigatran met the primary endpoint compared with 22% of those treated with standard of care (non-inferiority; p=0.0014). In addition, numerically fewer patients had VTE recurrence or progression of index thrombus when treated with dabigatran compared with standard of care.
In the secondary prevention study, VTE recurrence at 12 months occurred in 2.8% of patients with thrombophilia compared with no patients in the group with negative unknown thrombophilia.
These results are an important confirmation of what the results of DIVERSITY and the long-term dabigatran studies already suggested, Dr. Brandão said. The two original publications reported a higher than usual frequency of patients with thrombophilia, particularly in the long-term study, in whom a reason for long-term anticoagulation was required.
Limitations of the present study included the possibility for selection bias, as testing for thrombophilia status was not mandated in either study. In addition, some of the subgroups analyzed had only a small number of patients.
Dr. Brandão said that clinicians need to put these findings in perspective.
“At first glance, our findings report that pediatric patients with inherited or acquired thrombophilia were appropriately treated with dabigatran. This would represent the first DOAC pediatric study showing a comparable performance in relation to standard-of-care anticoagulation in children with thrombophilia, increasing the therapeutic options available,” Dr. Brandão said. “While the study included patients treated with dabigatran for up to 15 months . . . who had absent, minor, or major thrombophilia traits, additional investigation is required to clarify issues related to duration and intensity of anticoagulation according to time from the index venous thrombotic event and to severity of major inherited or acquired thrombophilia.”
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Brandão LR, Tartakovsky I, Albisetti M, et al. Dabigatran in the treatment and secondary prophylaxis of venous thromboembolism in children with thrombophilia [published online, 2022 Sept 23]. Blood Advances. doi: 10.1182/bloodadvances.2021005681.
