VTE Prevention in Acutely Ill Hospitalized Adults: What You Need to Know
The FDA approved betrixaban on June 23 as the first oral agent for the prevention of VTE prophylaxis in hospitalized medically ill adults
The FDA approved betrixaban (Bevyxxa, Portola Pharmaceuticals) on June 23, 2017 for the prevention of venous thromboemobolism (VTE) in hospitalized adults at risk for VTE due to restricted mobility or other VTE risk factors.
Betrixaban, an oral Factor Xa inhibiotor has not previously been FDA approved for any other indication. Patients should receive 160 mg on day 1 of prophylaxis and 80 mg once daily thereafter for up to 42 days. Patients with a CrCl 15-30 ml/min or who are taking P-gp inhibitors should receive 40 mg daily. The drug was approved in part due to the results of the Acute Medically Ill VTE Prevention with Extended Duration Betrixaban (APEX) study.
In this multinational, randomized, active-controlled trial, betrixaban was compared to enoxaparin (40 mg once daily) in more than 7,500 acutely ill hospitalized patients over the age of 40 years old with reduced mobility and VTE risk factors. The results were presented in 2 cohorts.
Cohort 1 included patients with a d-dimer level at least 2 times the upper limit of normal while cohort 2 included patients in cohort 1 in addition to patients over the age of 75 years. The occurance of the study's composite outcome (DVT, PE, or death from VTE as assessed at day 42) in the overall population, where the average age was approximately 76 years, was significantly less in the betrixaban group compared to enoxaparin (5.3% vs. 7%; RR 0.76; P=.006). The results were also significant in cohort 2 (5.6% vs. 7.1%; RR 0.8; P=.03), but not in cohort 1 (6.9% vs. 8.5%; RR0.81; P=.054). This suggests that there may potentially be an age-related benefit to the medication. However, a potential lack of power in cohort 1 may have resulted in failure to find a significant difference. Still, given the relative lack of knowledge of medications overall in geriatrics, the inclusion of a large number of older adults is encouraging. The net clinical benefit, defined as the composite primary outcome and the primary safety outcome was also significantly better in the overall population (P=.01) and cohort 2 (P=.05).
As would be expected, the most common adverse effect seen in the APEX study was bleeding. There was no difference in major bleeding in the overall population or either cohort, though betrixaban was associated with significantly more major of clinically relevant nonmajor bleeding in all populations evaluated. The overall incidence of bleeding was relatively low at 2.4% with betrixaban and 1.2% with enoxaparin.
Although betrixaban shows promise with efficacy in clinical studies, there are some practical and logistical barriers to integrating betrixaban into routine VTE prophylaxis. First, the drug was studied for 35-42 days, including post hospitalization.
Traditionally, hospitalized patients only receive VTE prophylaxis for the duration of the hospitalziation. The expense of the medication, not only to institutions, but to patients once discharged (to complete the duration of therapy) may prove to be cost prohibitive in comparison to the drugs significant, but overall modest benefit over enoxaparin.
Patients with extended mobility issues are often sent to skilled nursing facilities for a short duration, a care environment where betrixaban's role is unknown but would be interesting to evaluate. Although the option of an oral agent may be attractive to many patients, it is unclear how widespread its adoption will be into hosptial practice. The efficacy of betrixaban compared to current, and cheaper, prophylaxis agents in a more real world inpatient setting remains to be determined and until it is, it is hard to say how broad the role in therapy bretixaban will be given in clinical practice.
- Betrixaban. Food and Drug Administration. Available https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=208383
- Bevyxxa (betrixaban). Lexicomp Database. Available http://fco.factsandcomparisons.com/lco/action/doc/retrieve/docid/patch_f/6507859
- Cohen AT, Harrington RA, Goldhaber SZ, et al. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med. 2016;375:534-544