Written by Sam Parnell
Treatment with direct oral anticoagulants (DOACs) in pediatric patients appears to reduce venous thromboembolism (VTE) recurrence compared to standard of care, with no difference in major bleeding or serious adverse events. Prophylaxis with DOACs was comparable to standard of care and was associated with a nonsignificant reduction in VTE.
DOACs vs standard of care for pediatric VTE
Pediatric venous thromboembolism (VTE) is a relatively rare, but potentially life-threatening condition with increasing prevalence, especially in hospitalized children with complex medical problems. Standard of care for children with VTE has historically been limited to unfractionated heparin, low molecular weight heparin, fondaparinux, and vitamin K antagonists. These treatments are especially difficult for children due to the need for IV access, subcutaneous injections, dietary restrictions, drug-drug interactions, and regular monitoring. Could direct oral anticoagulants (DOACs) offer a better alternative to manage pediatric VTE?
This was a systematic review and meta-analysis of RCTs (7 studies in the systematic review and 6 in the meta-analysis) comparing DOACs to standard of care (SOC) for children less than 18 years old for treatment and prophylaxis of VTE. Treatment of VTE with DOACs was associated with a significant reduction in VTE recurrence compared to SOC (OR = 0.42, 95%CI 0.19–0.94). All-cause mortality for VTE treatment was similar for DOACs vs SOC, and no deaths were reported for any of the cardiac disease patients receiving VTE prophylaxis.
Primary VTE prophylaxis with DOACs was comparable to SOC, with a non-significant reduction in VTE recurrence (OR 0.22, 95%CI 0.03–1.55). There was no difference in major bleeding, any bleeding, or serious adverse events when comparing DOACs to SOC for prophylaxis and treatment of VTE. However, VTE treatment with DOACs was associated with increased rates of discontinuation due to adverse events compared to SOC (OR 2.70, 95%CI 1.02–7.15), possibly related to the open-label design of the trials.
This study was limited due to the relatively small sample size of the included studies and heterogeneity of the patient population (age, comorbidities, indication for treatment, definition of SOC, type of DOAC medication, etc.). However, the data appear promising that DOACs may be more efficacious for VTE treatment and comparable to SOC for VTE prophylaxis, without an increase in bleeding or major adverse events.
How will this change my practice?
The FDA has approved rivaroxaban and dabigatran for treatment and prevention of VTE in children, and these medications seem to be safe, effective, and relatively easy to administer. I rarely prescribe DOACs for pediatric patients in the ED. However, this systematic review and meta-analysis makes me more comfortable with the practice. Based on this information, I will be more likely to discuss DOAC therapy with consultants, pediatric patients, and their families in the future.
Efficacy and safety of direct oral anticoagulants in the pediatric population: a systematic review and a meta-analysis. J Thromb Haemost. 2023 Jul 20:S1538-7836(23)00573-1. doi: 10.1016/j.jtha.2023.07.011. Epub ahead of print.