Real-world data capture low use of DOACs among children

Use of direct oral anticoagulants (DOACs) appears to be limited in paediatric clinical practice, with heparins being the most prescribed, followed by warfarin.

In an analysis of more than 51 million children with at-risk conditions from three databases in the United States (ie, CCAE*, MDCD**, and Optum⁺) the overall use of anticoagulants was infrequent in the paediatric population. Only 49,000 children received anticoagulant therapies. [Clin Ther 2021;doi:10.1016/j.clinthera.2021.09.021]

Heparins, such as unfractionated heparin, enoxaparin, nadroparin, and dalteparin, were used most often overall (n=46,229) and in the youngest patients. Among children who received warfarin (n=1,811), the majority (>54 percent) were aged 12 to <18 years, 9–19 percent were aged 7 to <12 years, and 15–23 percent were aged 2 to <7 years.

Meanwhile, all DOACs (n=1,442), particularly rivaroxaban (n=778) and apixaban (n=216), were uncommon and mainly dispensed in older children (12 to <18 years).

Among children exposed to anticoagulants, the unadjusted incidence rates of venous thromboembolism (VTE) ranged from 30.8 to 34.0 per 1,000 person-years of exposure for all DOACs, from 21.6 to 46.2 per 1,000 person-years for warfarin, and from 6.0 to 7.3 per 1,000 person-years for heparins.

On the other hand, major bleeding occurred at an incidence rate of 0–4.9 per 1,000 person-years with all DOACs, 4.3–6.7 per 1,000 person-years with warfarin, and 3.7–4.6 per 1,000 person-years with heparins.

In a subpopulation of 4,594 children with a history of a Fontan procedure, anticoagulation therapy was used in a similar manner in these patients compared with the overall paediatric population. Likewise, VTE occurred more frequently than major bleeding in this subgroup.

Common conditions that were identified in the 183 days prior to and including the drug exposure were cerebral vein and sinus thrombosis (CVST), VTE, fractures, and others (eg, pain, injury, and arthropathy).

The data on the incidence of VTE and major bleeding for each type of anticoagulant, according to the investigators, “are not intended to imply causality or to be used comparatively, given the lack of adjustments for confounding variables between drug exposure populations and the inability to differentiate between new and recurrent events.”

Furthermore, they explained that most anticoagulants currently used in clinical practice are not approved by the US Food and Drug Administration in the paediatric population. When prescribing, most paediatricians rely on adult data and the limited available paediatric data.

“Therefore, in our analysis, the condition before the index anticoagulant exposure may be associated with the use of the anticoagulant, but such correlations should be carefully interpreted,” the investigators said.

Results from clinical trials evaluating DOACs in the paediatric population, and subsequent approvals of paediatric product labelling updates, are expected in the next 2 years. The investigators believe that the present descriptive real-world data may provide a baseline understanding of current prescribing patterns and outcomes associated with the use of DOACs and other anticoagulants in routine paediatric clinical practice.

*IBM MarketScan Commercial Claims and Encounters Database

**IBM MarketScan Multi-State Medicaid Database

⁺Optum's de-identified Clinformatics Data Mart Database–Socio-Economic Status