Related Experiment Video
Updated: Jul 9, 2025
The WATCHMAN Left Atrial Appendage Closure Device for Atrial Fibrillation
Published on: February 28, 2012
Apixaban for Prevention of Thromboembolism in Pediatric Heart Disease
R Mark Payne1, Kristin M Burns2, Andrew C Glatz3
1Riley Hospital for Children, Wells Center for Pediatric Research, Department of Pediatrics, Division of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Insights
Apixaban showed infrequent bleeding and no thromboembolism in children with heart disease, supporting its use for thromboprophylaxis. Pediatric apixaban pharmacokinetics matched adult levels, suggesting efficacy.
Area of Science:
- Pediatric Cardiology
- Pharmacology
- Hematology
Background:
- Children with heart disease often need anticoagulation for thromboprophylaxis.
- Current treatments like vitamin K antagonists and low-molecular-weight heparin have drawbacks.
Purpose of the Study:
- To evaluate the safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of apixaban in pediatric patients with heart disease.
- Apixaban is an oral, direct factor Xa inhibitor being investigated as an alternative anticoagulant.
Main Methods:
- A Phase 2, open-label, randomized trial comparing apixaban to standard of care (SOC) in children (28 days to <18 years) with heart disease.
- Participants received either apixaban or SOC for one year, with intention-to-treat analysis.
Main Results:
- 192 participants were randomized (129 apixaban, 63 SOC).
- Bleeding events were infrequent: 0.8% in the apixaban group vs. 4.8% in the SOC group.
- Apixaban's pediatric PK steady-state exposures were consistent with adult levels; no thromboembolic events or deaths occurred.
Conclusions:
- Bleeding and thromboembolism were infrequent with both apixaban and SOC in this pediatric trial.
- Apixaban PK data align with adult studies, suggesting potential efficacy.
- Apixaban is a viable alternative to SOC for thromboprophylaxis in pediatric heart disease.
Background:
Children with heart disease frequently require anticoagulation for thromboprophylaxis. Current standard of care (SOC), vitamin K antagonists or low-molecular-weight heparin, has significant disadvantages.
Objectives:
The authors sought to describe safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of apixaban, an oral, direct factor Xa inhibitor, for prevention of thromboembolism in children with congenital or acquired heart disease.
Methods:
Phase 2, open-label trial in children (ages, 28 days to <18 years) with heart disease requiring thromboprophylaxis. Randomization 2:1 apixaban or SOC for 1 year with intention-to-treat analysis.
Primary Endpoint:
a composite of adjudicated major or clinically relevant nonmajor bleeding. Secondary endpoints: PK, pharmacodynamics, quality of life, and exploration of efficacy.
Results:
From 2017 to 2021, 192 participants were randomized, 129 apixaban and 63 SOC. Diagnoses included single ventricle (74%), Kawasaki disease (14%), and other heart disease (12%). One apixaban participant (0.8%) and 3 with SOC (4.8%) had major or clinically relevant nonmajor bleeding (% difference -4.0 [95% CI: -12.8 to 0.8]). Apixaban incidence rate for all bleeding events was nearly twice the rate of SOC (100.0 vs 58.2 per 100 person-years), driven by 12 participants with ≥4 minor bleeding events. No thromboembolic events or deaths occurred in either arm. Apixaban pediatric PK steady-state exposures were consistent with adult levels.
Conclusions:
In this pediatric multinational, randomized trial, bleeding and thromboembolism were infrequent on apixaban and SOC. Apixaban PK data correlated well with adult trials that demonstrated efficacy. These results support the use of apixaban as an alternative to SOC for thromboprophylaxis in pediatric heart disease. (A Study of the Safety and Pharmacokinetics of Apixaban Versus Vitamin K Antagonist [VKA] or Low Molecular Weight Heparin [LMWH] in Pediatric Subjects With Congenital or Acquired Heart Disease Requiring Anticoagulation; NCT02981472).
Related Concept Videos
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
01:18Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...