The optimum duration of anticoagulation for children and young people under 21 with acute provoked venous thromboembolism is six weeks rather than the three months recommendation based on adult data, a major study has shown.
A multicentre randomised clinical trial that included 417 patients with provoked venous thromboembolism – including Australian centres – showed that anticoagulant therapy for six weeks was non-inferior to three months based on the trade-off between recurrent venous thromboembolism risk and bleeding risk.
In the Kids-DOTT study, published in JAMA, anticoagulant therapy for six weeks (n = 207) vs three months (n = 210) resulted in symptomatic recurrent VTE in 0.66% vs 0.70% of patients, respectively, and clinically relevant bleeding events in 0.65% vs 0.70% within one year.
Noninferiority between the two groups was demonstrated based on absolute risk differences in recurrent VTE and clinically relevant bleeding events.
Adverse events occurred in 26% of patients in the six-week anticoagulant therapy group and in 32% of patients in the three-month anticoagulant therapy group; the most common events being fever (1.9% and 3.4%, respectively).
Lead author of the study, Dr Neil Goldenberg of the Johns Hopkins All Children’s Hospital, Florida, described the results as “practice changing” because until now there has been no evidence from children to guide decisions on the optimum duration of anticoagulation in the treatment of first-episode venous thromboembolism
“Previous treatments relied on trials from the 1990s in older adult VTE patients, so it was important for us to find a better solution for the growing number of infants, children teens and young adults affected by VTE,” he said.
“Shorter treatment should not only result in significant savings in health care costs, but more importantly, is expected to improve quality of life for patients and families. Being on anticoagulant medications, … means having to worry about and take significant precautions against bleeding complications. Coming off of anticoagulant medications in half the amount of time as in the past means being able to return to normal routines, activities and sports much sooner.”
Dr Goldenberg said that the findings, along with other recent data, suggested that the risks of recurrent VTE and clinically relevant bleeding events in young patients were lower than previously reported from observational studies—particularly among those with provoked VTE
“This may reflect experience gained in paediatric VTE management and improved ability to distinguish provoked from unprovoked VTE in children and young adults,” they wrote.
The study authors noted that VTE occurs in about 1 in 200 hospitalised children, and about 1 in 50 children hospitalized with critical illnesses, making it one of the most common hospital-acquired paediatric conditions.
In addition, for more than the past year, children’s hospitals have been seeing a spike in VTE attributable to acute COVID-19 infection, especially among those who develop the multisystem inflammatory syndrome in children (known as MIS-C).
However they cautioned that the shorter duration of anticoagulation would not be suitable for the 5-10% of patients under 21 whose VTE are unprovoked, and such patients require longer than three months of anticoagulants.
Likewise the Kids-DOTT trial criteria excluded children whose blood clots with persistent antiphospholipid antibodies and those whose thrombi were completely occlusive by repeat ultrasound at the six-week follow-up mark, for whom the historical conventional duration of anticoagulation should still be considered as the standard.
And because few patients with cancer or whose VTE involved pulmonary embolism were enrolled in the trial, the findings of the Kids-DOTT trial also do not apply to patients with these conditions, they said.
“Yet, the vast majority of patients younger than 21 years of age with VTE do not have cancer, pulmonary embolism, or complete occlusion at six weeks follow-up, and for this reason the findings of the Kids-DOTT trial are far-reaching,” they said.