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Effects of apixaban versus vitamin K antagonists and low molecular weight heparin in pediatric cardiac patients: exploratory biomarker analysis from SAXOPHONE a multicentre randomized clinical trial

1University of Alberta, Edmonton, Alberta, Canada, 2Bristol Myers Squibb, Lawrence Township, New Jersey, United States, 3Bristol Myers Squibb, Inc, Lawrence Township, New Jersey, United States, 4Indiana University School of Medicine, Dept of Pediatrics (Cardiology), Indianapolis, Indiana, United States, 5 Medical University of Vienna, Austria, Vienna, Wien, Austria, 6Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United States, 7Bristol Myers Squibb, Inc., Lawrence Township, New Jersey, United States, 8Dept of Paediatrics, Univ of Melbourne, and Royal Children's Hospital, Melbourne, Victoria, Australia, 9Heart Development and Structural Diseases Branch / Division of Cardiovascular Sciences, Bethesda, Maryland, United States, 10Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada

Abstract Number: PB0254

Meeting: ISTH 2022 Congress

Theme: Pediatrics » Thrombosis in Neonates and Children

Background: The safety and efficacy of apixaban for venous thromboembolism (VTE) prophylaxis was assessed in pediatric patients with congenital or acquired heart disease in a multinational trial (SAXOPHONE). Patients in need of extended thromboprophylaxis were randomized 2:1 to receive either apixaban or standard of care (SOC) which was either VKA or LMWH.

Aims: An exploratory biomarker analysis was conducted to better understand mechanisms of the anticoagulation effect in pediatric patients.

Methods: Plasma samples were obtained from study participants at baseline (screening or pre-dose on Day1), after 2 weeks and 6 months of treatment. Samples were analyzed for FVIII, Fibrinogen, Protein C, Protein S, and D-Dimer by ELISA. Ex-vivo thrombin generation was measured using Technoclone TGA. Data from 182 participants were included [apixaban (n=123) and SOC (n=59)].

Results: Fibrinogen and FVIII levels showed no difference between treatment groups. Protein C and Protein S were statistically significantly increased in apixaban-treated patients when compared to those who received SOC (p < 0.005, Table 1). D-Dimer showed a trend to decrease at Month 6 in both groups without significant treatment differences. Endogenous thrombin potential and peak thrombin levels were higher in the apixaban group compared to SOC. The lag time and time to peak were significantly increased in the apixaban arm compared to SOC (Figure 1).

Conclusion(s): D-Dimer trended toward a decrease in both apixaban and SOC groups at Month 6 suggesting a reduction in thrombin activation. Protein C and S levels increased in the apixaban group compared to SOC. Thrombin generation patterns differed between the two groups, with apixaban showing more prominent prolongation of lag time and time to peak compared to SOC. No difference was observed in the rate of thrombin generation between groups. SOC treatment reduced the thrombin generated and decreased endogenous thrombin potential compared with apixaban. Additional subgroup analyses based on clinical characteristics are in progress.

Table 1

Biomarker levels pre-study-medication and during treatment at Week 2 and Month 6 -mean±sd-

Figure 1

Representative graphs of thrombin generation in apixaban and SOC groups

To cite this abstract in AMA style:

Aborkhees G, Wang Z, Yao C, Reedy A, Payne R, Male C, Glatz A, Dyme J, Barr A, He A, Monagle P, Burns K, Schafer P, Mitchell L. Effects of apixaban versus vitamin K antagonists and low molecular weight heparin in pediatric cardiac patients: exploratory biomarker analysis from SAXOPHONE a multicentre randomized clinical trial [abstract]. https://abstracts.isth.org/abstract/effects-of-apixaban-versus-vitamin-k-antagonists-and-low-molecular-weight-heparin-in-pediatric-cardiac-patients-exploratory-biomarker-analysis-from-saxophone-a-multicentre-randomized-clinical-trial/. Accessed October 1, 2023.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/effects-of-apixaban-versus-vitamin-k-antagonists-and-low-molecular-weight-heparin-in-pediatric-cardiac-patients-exploratory-biomarker-analysis-from-saxophone-a-multicentre-randomized-clinical-trial/