Use of apixaban in children awaiting heart transplantation

Abstract

BackgroundThe use of apixaban in the pediatric cardiac population is expanding. We describe our apixaban dosing and monitoring strategy in children and young adults awaiting heart transplantation, along with outcomes related to bleeding and thrombosis during wait‐list and early post‐transplant periods.MethodsThis study is a retrospective, single‐center analysis of all patients receiving apixaban while awaiting cardiac transplantation. Weight‐based dosing was monitored with peak drug‐specific anti‐Xa chromogenic analysis. Significant post‐operative bleeding defined by chest tube output or need for surgical intervention.ResultsFrom September 2020 to December 2022, 19 patients, median age 13.5 years (6.1, 15.8 years), weighing 48.9 kg (15.4, 67.6) received apixaban while awaiting transplant. Indication for apixaban was prophylaxis (n = 18, 3 with ventricular assist devices) and treatment of thrombus (n = 1). There were no clinically relevant non‐major or major bleeding, nor thrombotic events while awaiting transplant. The median time from last apixaban dose to arrival in the operating room was 23.2 h (15.6–33.8), with median random apixaban level of 37 ng/mL (28.3, 59), 6.3 h (4.8, 8.4) prior to arrival in the operating room. In this study, 32% of patients had significant post‐operative bleeding based on chest tube output post‐transplant or need for intervention. No patients meeting criteria for significant post‐operative bleeding were thought to be attributable to apixaban.ConclusionsCareful use of apixaban can be safe and effective while awaiting heart transplant. There was no appreciable increase in peri‐operative bleeding. The use of apixaban is promising in providing safe, predictable and efficacious anticoagulation while avoiding additional patient stressors.

Leveling the playing field: The role of level‐based dosing in pediatric anticoagulation management

“…[25][26][27][28] In our Cardiac Antithrombosis Program, we utilize peak apixaban levels to guide dosing as per patient risk of thrombosis/bleeding and indication. 29,30 Similar to adults, we have found in our clinical practice that apixaban has a wide margin of safety and efficacy, resulting in clot resolution and absence of bleeding adverse events across wide range of apixaban levels. 29 On the basis of this, one could argue that the apixaban level offers no diagnostic purpose.…”

Real‐world experience of direct oral anticoagulant use in a single pediatric center

“…Reports on efficacy (recurrent thrombosis rate) and safety (bleeding rate) in children treated with DOACs are limited to the pivotal clinical trials, a retrospective/prospective study from the American Thrombosis Hemostasis Network (ATHN) and four singlecenter studies, each looking at single DOAC for safety and efficacy. [5][6][7][8][9][10][11] Of the four single-center studies, two reviewed apixaban use in those awaiting a heart transplant and those with cardiac disease investigating both treatment and prophylactic use, and the other two reviewed rivaroxaban one in children less than 16 years old and the other in cancer-associated thrombus. [8][9][10] Thus, data on DOACs for VTE remain scarce.…”

“…[5][6][7][8][9][10][11] Of the four single-center studies, two reviewed apixaban use in those awaiting a heart transplant and those with cardiac disease investigating both treatment and prophylactic use, and the other two reviewed rivaroxaban one in children less than 16 years old and the other in cancer-associated thrombus. [8][9][10] Thus, data on DOACs for VTE remain scarce. Before their FDA approval, DOACs have been used "off-label" in children on an individualized basis, subject to approval from individual insurance plans.…”

“…The use of DOACs in the pediatric population for both treatment and prophylaxis has grown in recent years as new evidence becomes available, and two DOACs, rivaroxaban and dabigatran, have recently been approved for use in children. Reports on efficacy (recurrent thrombosis rate) and safety (bleeding rate) in children treated with DOACs are limited to the pivotal clinical trials, a retrospective/prospective study from the American Thrombosis Hemostasis Network (ATHN) and four single‐center studies, each looking at single DOAC for safety and efficacy 5–11 . Of the four single‐center studies, two reviewed apixaban use in those awaiting a heart transplant and those with cardiac disease investigating both treatment and prophylactic use, and the other two reviewed rivaroxaban one in children less than 16 years old and the other in cancer‐associated thrombus 8–10 .…”

“…Patients were on various durations of therapy ranging from 6 weeks to extended anticoagulation therapy depending on their clinical status, risk factors, and thrombus resolution, with a median duration of DOAC therapy of 6 months. Fifteen percent(10) of patients transitioned to secondary thromboprophylaxis after completing treatment for their VTE, while the remaining 85% (55) discontinued anticoagulation. The mean and median durations of follow-up for the cohort were 32 and 11.5 months, respectively (range of 12−120 months).…”