PB0254 - 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

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

GA

Ghada A. Aborkhees, MD,MSc

Graduate student
University of Alberta
Edmonton, Alberta, Canada

Co-Author(s)

ZW

Zhaoqing Wang

Sr. Director
Bristol Myers Squibb
Lawrence Township, New Jersey, United States
CY

Chen Yao

Principal scientist
Bristol Myers Squibb
Lawrence Township, New Jersey, United States
AR

Alison M. Reedy

Clinical scientist
Bristol Myers Squibb, Inc
Lawrence Township, New Jersey, United States
RP

R.Mark Payne

Physician
Indiana University School of Medicine, Dept of Pediatrics (Cardiology)
Indianapolis, Indiana, United States
Christoph Male, MD, MSc

Head of the Pediatric Hemostasis & Thrombosis Unit
Department of Paediatrics, Medical University of Vienna, Vienna, Austria.
Vienna, Wien, Austria
AG

Andrew C. Glatz

Interventional cardiologist
Children’s Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
JD

Joshua L. Dyme

Senior Clinical Trial Physician
Bristol Myers Squibb
Lawrence Township, New Jersey, United States
AB

Amy J. Barr

Senior Research Technician
University of Alberta
Edmonton, Alberta, Canada
AH

Aiqing He

Principal Scientist
Bristol Myers Squibb
Lawrence Township, New Jersey, United States
Paul Monagle, MD

Professor
Haematology Research, Murdoch Children's Research Institute
Melbourne, Victoria, Australia
KB

Kristin M. Burns

Program officer
Heart Development and Structural Diseases Branch / Division of Cardiovascular Sciences
Bethesda, Maryland, United States
PS

Peter Schafer

Scientific vice president
Bristol Myers Squibb
Lawrence Township, New Jersey, United States
LM

Lesley G. Mitchell, MD

Professor
University of Alberta, Division of Pediatric Hematology/Oncology
Edmonton, Alberta, Canada

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.