Extended-duration betrixaban versus shorter-duration enoxaparin for venous thromboembolism prophylaxis in critically ill medical patients: an APEX trial substudy.

Abstract

PURPOSE:

To assess the efficacy and safety of betrixaban for venous thromboembolism (VTE) prophylaxis among critically ill patients.

METHODS:

The APEX trial randomized 7513 acutely ill hospitalized patients to betrixaban for 35-42 days or enoxaparin for 10 ± 4 days. Among those, 703 critically ill patients admitted to the intensive care unit were included in the analysis, and 547 patients who had no severe renal insufficiency or P-glycoprotein inhibitor use were included in the full-dose stratum. The risk of VTE, bleeding, net clinical benefit (composite of VTE and major bleeding), and mortality was compared at 35-42 days and at 77 days.

RESULTS:

At 35-42 days, extended betrixaban reduced the risk of VTE (4.27% vs 7.95%, P = 0.042) without causing excess major bleeding (1.14% vs 3.13%, P = 0.07). Both VTE (3.32% vs 8.33%, P = 0.013) and major bleeding (0.00% vs 3.26%, P = 0.003) were decreased in the full-dose stratum. Patients who received betrixaban had more non-major bleeding than enoxaparin (overall population: 2.56% vs 0.28%, P = 0.011; full-dose stratum: 3.32% vs 0.36%, P = 0.010). Mortality was similar at the end of study (overall population: 13.39% vs 16.19%, P = 0.30; full-dose stratum: 13.65% vs 16.30%, P = 0.39).

CONCLUSIONS:

Compared with shorter-duration enoxaparin, critically ill medical patients who received extended-duration betrixaban had fewer VTE without more major bleeding events. The benefit of betrixaban was driven by preventing asymptomatic thrombosis and offset by an elevated risk of non-major bleeding. The APEX trial did not stratify by intensive care unit admission and the present study included a highly selected population of critically ill patients. These hypothesis-generating findings need to be validated in future studies.

CLINICAL TRIAL REGISTRATION:

http://www.clinicaltrials.gov . Unique identifier: NCT01583218.

• Authors: Gerald Chi, C Michael Gibson, Arzu Kalayci, Alexander T Cohen, Adrian F Hernandez, Russell D Hull, Farima Kahe, Mehrian Jafarizade, Sadaf Sharfaei, Yuyin Liu, Robert A Harrington, Samuel Z Goldhaber
• Journal: Intensive care medicine (Intensive Care Med) Vol. 45 Issue 4 Pg. 477-487 (04 2019) ISSN: 1432-1238 [Electronic] United States
• PMID: 30778649 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Anticoagulants
• Benzamides
• Enoxaparin
• Factor Xa Inhibitors
• Pyridines
• betrixaban

Topics

• Adult
• Aged
• Aged, 80 and over
• Anticoagulants (standards, therapeutic use)
• Benzamides (standards, therapeutic use)
• Critical Illness
• Enoxaparin (standards, therapeutic use)
• Factor Xa Inhibitors (standards, therapeutic use)
• Female
• Humans
• Male
• Middle Aged
• Pre-Exposure Prophylaxis (methods, standards)
• Pyridines (standards, therapeutic use)
• Risk Factors
• Time Factors
• Venous Thromboembolism (drug therapy, prevention & control)