Background Elevated
D-dimer concentrations are associated with an increased risk of
venous thromboembolism (VTE). However, they may also provide prognostic value. The present analysis sought to study the association of
D-dimer levels with VTE event rates and the efficacy of
betrixaban versus
enoxaparin in the APEX trial. Methods Hospitalized acutely medically ill subjects ( n = 7,513) were randomized in a double-dummy double-blind fashion to either extended-duration oral
betrixaban (80 mg once daily for 35-42 days) or standard dose subcutaneous
enoxaparin (40 mg once daily for 10 ± 4 days) for venous thromboprophylaxis.
D-dimer was assessed using a central core laboratory measurement. Results For every 0.25 µg/mL increase in
D-dimer concentration, there was a 2% increase in the relative risk of experiencing the primary efficacy endpoint (asymptomatic
deep vein thrombosis [DVT], symptomatic DVT, nonfatal
pulmonary embolism, or VTE-related death) in both the
betrixaban ( p < 0.001) and
enoxaparin ( p < 0.001) treatment arms. Among
D-dimer-positive (≥ 2 × upper limit of normal; corresponding to ≥ 1.00 µg/mL) subjects, extended-duration
betrixaban reduced the risk of experiencing the primary efficacy outcome (5.4% [ n = 124] vs. 7.6% [ n = 170]; odds ratio = 0.69; 95% confidence interval: 0.55-0.88; absolute risk reduction = 2.2%, number needed to treat = 46, p = 0.003). There was no interaction between
D-dimer and the treatment effect ( p int = 0.53). Conclusion Extended-duration
betrixaban was superior to standard-duration
enoxaparin, irrespective of
D-dimer level at baseline. To prevent one VTE event, 46
D-dimer-positive patients would need to be treated with
betrixaban.