The Safety and Efficacy of Full Versus Reduced Dose Betrixaban in the Acute Medically Ill VTE (Venous Thromboembolism) Prevention with Extended Duration Betrixaban (APEX) Trial

Background The Acute Medically Ill VTE (Venous Thromboembolism) Prevention with Extended Duration Betrixaban (APEX) trial assessed the safety and efficacy of extended-duration thromboprophylaxis using betrixaban versus standard dosing of enoxaparin among acutely ill medical patients. The 80 mg betri...

Full description

Saved in:
Bibliographic Details
Published in:The American heart journal 2017-03, Vol.185, p.93-100
Main Authors: Gibson, C. Michael, Halaby, Rim, Korjian, Serge, Daaboul, Yazan, Arbetter, Douglas F, Yee, Megan K, Goldhaber, Samuel Z, Hull, Russel, Hernandez, Adrian F, Gold, Alex, Wiens, Brian, Leeds, Janet, Harrington, Robert A, Cohen, Alexander T
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Anticoagulants
Anticoagulants - therapeutic use
Benzamides - administration & dosage
Bleeding
Cardiovascular
Clinical trials
Double-Blind Method
Drug dosages
Effectiveness
Embolism
Enoxaparin - therapeutic use
Factor Xa Inhibitors - administration & dosage
Female
Glycoproteins
Health risk assessment
Hemorrhage - chemically induced
Hospitalization
Humans
Kidney transplantation
Laboratories
Male
P-Glycoprotein
Pharmacokinetics
Pharmacology
Population
Prevention
Pulmonary Embolism - prevention & control
Pyridines - administration & dosage
Reduction
Renal insufficiency
Risk
Risk management
Risk reduction
Safety
Studies
Thromboembolism
Thrombosis
Venous Thromboembolism - prevention & control
Venous Thrombosis - prevention & control
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background The Acute Medically Ill VTE (Venous Thromboembolism) Prevention with Extended Duration Betrixaban (APEX) trial assessed the safety and efficacy of extended-duration thromboprophylaxis using betrixaban versus standard dosing of enoxaparin among acutely ill medical patients. The 80 mg betrixaban dose was halved to 40 mg among subjects with severe renal insufficiency and those receiving a concomitant strong P-glycoprotein (P-gp) inhibitor. Methods This analysis assessed the pharmacokinetics, efficacy and safety of full (80 mg) and reduced dose (40 mg) betrixaban relative to enoxaparin in the APEX trial. Results The median concentration of betrixaban among subjects administered the 80 mg dose was higher than that of the 40 mg dose (19 ng/ml vs 11 ng/ml, P < .001). In the primary analysis Cohort 1 (D-dimer ≥2X ULN), the primary efficacy outcome (PEO) (asymptomatic proximal DVT, symptomatic proximal or distal DVT, symptomatic nonfatal PE, or VTE-related death) was significantly reduced among subjects treated with 80 mg of extended dose betrixaban vs enoxaparin [6.27% (95/1516) vs 8.39% (130/1549), RRR = 0.26 (0.04–0.42), P = .023]; and similarly in the entire PEO population [4.87% (122/2506) vs 7.06% (181/2562), RRR = 0.30 (0.13–0.44), P = .001]. There was no difference in the primary outcome for subjects treated with 40 mg betrixaban dose vs enoxaparin across Cohorts. Additionally, there was no excess of major bleeding associated with either betrixaban dose compared with enoxaparin. Conclusions The 80 mg betrixaban dose achieves higher serum concentrations than the 40 mg dose and is associated with improved efficacy across all cohorts relative to standard dose enoxaparin, without an excess risk of major bleeding in the management of medically ill patients.
ISSN:0002-8703
1097-6744
DOI:10.1016/j.ahj.2016.12.004