Edoxaban Noninferior to Standard of Care for Preventing TE in Pediatric Cardiac Disease

Edoxaban therapy for prevention of thromboembolism in pediatric patients with cardiac disease is safe and effective.

Once daily oral edoxaban is safe and effective for the prevention of thromboembolism (TE) among pediatric patients with cardiac disease, according to results of a study presented at the American Heart Association (AHA) Scientific Sessions 2022, held from November 5th through 7th, in Chicago, Illinois.

In the setting of pediatric cardiac disease, the standard of care (SOC) anticoagulation strategies are low molecular weight heparin or vitamin K antagonists. However, drug delivery by injection and food and drug interactions may be significant treatment barriers for some patients.

To test the direct oral anticoagulant edoxaban against SOC, the phase 3, multinational, prospective, randomized, open-label trial ENNOBLE-ATE (ClinicalTrails.gov Identifier: NCT00687882), was conducted between 2018 and 2021 in 15 countries. Pediatric patients (N=168) with cardiac disease were randomly assigned in a 2:1 ratio to receive age- and weight-adjusted oral edoxaban (n=109) or SOC (n=58) for 3 months followed by the option to switch or continue using edoxaban for 9 months. The primary outcome for this study was clinically-relevant bleeding events, defined using the International Society on Thrombosis and Haemostasis criteria.

The mean patient age was 8 years, 65% were boys, and 71% were White. The cardiac disease diagnoses included Kawasaki disease, heart failure, and congenital heart defects.

During the first 3 months of the study, the 2 cohorts had a similar clinically-relevant bleeding rate, in which 1 patient from each cohort experienced a nonmajor bleeding event.

Treatment-emergent adverse events occurred among 46.8% of edoxaban recipients and 41.4% of SOC recipients, which included common cold, sniffles, and upset stomach events. One patient in the SOC cohort had 2 TE events, a deep venous TE with pulmonary embolism.

During the extension period, among the 152 edoxaban recipients, 1 patient had a trauma-related clinically-relevant bleeding event, 2 had strokes, and 2 had a coronary artery thrombosis and/or myocardial infarction.

This study found that once-daily oral edoxaban had similar safety and efficacy profiles as SOC for preventing TE among children with cardiac disease. Due to the oral delivery method and the potential food and drug interactions that can occur with warfarin, edoxaban may be a more favorable treatment strategy in this patient population. However, edoxaban is not currently approved by the Food and Drug Administration for use among children.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

References:

Portman MA, Jacobs JP, Newburger JW, et al. Edoxaban for pediatric patients with cardiac diseases: a randomized, open-label, multicenter study. Presented at: The American Heart Association (AHA) Scientific Sessions 2022; November 5-7, 2022; Chicago, IL. Abstract #316.