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Betrixaban may reduce VTE risk in certain patients with acute illness
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The primary efficacy outcome of the APEX trial was not met, but exploratory analyses suggest that extended-duration thromboprophylaxis with Factor Xa inhibitor betrixaban may reduce venous thromboembolism risk in patients with acute illness.
Alexander T. Cohen, MD, from the department of hematological medicine, Guy’s and St. Thomas’ Hospitals, London, and colleagues conducted a randomized, double blind, double dummy, active-controlled, clinical trial to evaluate the efficacy and safety of betrixaban (Portola Pharmaceuticals) in preventing VTE in patients with acute illness in comparison with enoxaparin.
Alexander T. Cohen
Betrixaban is not yet approved for use in the United States.
To be eligible for the study, patients needed to be aged at least 40 years, be hospitalized for acute illness for less than 96 hours and have VTE risk factors.
Researchers randomly assigned 7,513 patients to subcutaneous enoxaparin 40 mg per day for 10 days plus oral betrixaban placebo once daily for 35 to 42 days or to subcutaneous enoxaparin placebo once daily for 10 days plus oral betrixaban (loading dose of 160 mg and 80 mg per day for 35 to 42 days). Follow-up lasted for 30 days after assessment on day 42.
VTE risk
The primary efficacy outcome was a composite of asymptomatic proximal deep vein thrombosis between day 32 and day 47, symptomatic proximal or distal DVT, symptomatic nonfatal pulmonary embolism, or death from VTE between day 1 and day 42. The primary safety endpoint was major bleeding up to 7 days after medication was discontinued.
In the primary trial cohort of patients with an elevated D-dimer level, the primary efficacy endpoint was reached in 6.9% of the betrixaban group and 8.5% of the enoxaparin group (RR in the betrixaban group = 0.81; 95% CI, 0.65-1; P = .054).
“This first test in the sequence of cohorts did not meet the prespecified threshold for statistical significance; therefore, all subsequent prespecified efficacy outcomes were considered to be exploratory and were not used to draw conclusions regarding statistical significance,” Cohen and colleagues wrote.
In the secondary cohort of patients with an elevated D-dimer level or aged at least 75 years, the primary endpoint occurred in 5.6% of the betrixaban group and 7.1% of the enoxaparin group (RR = 0.8; 95% CI, 0.66-0.98).
In the overall population, the primary efficacy endpoint was met in 5.3% of those assigned betrixaban and 7% of those assigned enoxaparin (RR = 0.76; 95% CI, 0.63-0.92).
Data also revealed that major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (RR = 1.19; 95% CI, 0.67-2.12).
Net clinical benefit
Overall net clinical benefit, a composite of all primary efficacy and safety endpoints, was observed in 5.8% of the betrixaban group and 7.3% of the enoxaparin group (RR = 0.78; 95% CI, 0.65-0.95).
According to Cohen and colleagues, despite there being “no significant between-group difference in the prespecified primary efficacy outcome among the patients with an elevated D-dimer level,” data from the exploratory analyses suggested that betrixaban may reduce VTE risk. – by Tracey Romero
Disclosure: The study was funded by Portola Pharmaceuticals. Cohen reports financial ties with Bayer Healthcare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Janssen, Johnson & Johnson, Sanofi and X01. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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