Extended thromboprophylaxis with betrixaban in acutely ill medical patients.
Thromboprophylaxis during an episode of acute medical illness is effective preventing venous thromboembolism. Despite a somewhat increased risk for venous thromboembolism also in the period after the acute illness, current guidelines do not recommend extended thromboprophylaxis.
In this randomised double-blind (double-dummy) study, extended prophylactic anticoagulation (35-42 days) with betrixaban, a novel oral anti-factor Xa agent, was compared with a conventional regimen of enoxaparin 40 mg for 10 ± 4 days in 7513 patients with an acute medical illness.The incidence of symptomatic and non-symptomatic venous thromboembolism was analysed in three prospectively defined cohorts, i.e. 1) those with an elevated D-dimer level, 2) those with an elevated D-dimer level or aged 75 years or older, and 3) the overall cohort.
In group 1, the incidence of venous thromboembolism was 6.9% in patients receiving betrixaban and 8.5% in those receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P = 0.054), hence a difference close to but not reaching statistically significance. In groups 2 and 3, the relative risks were 0.80 and 0.76, respectively, in favour of the betrixaban group, and both differences were statistically significant. Major bleeding rates (0.7-0.8%) did not differ between the two treatment groups.
The obvious strength of this study is the relatively large study population and the rigorous study methodology. Having said that, the study design is a bit puzzling. In fact, the comparison is not only between conventional and extended thromboprophylaxis but also between two different anticoagulant regimens. In addition, the results are rather disappointing as the beneficial effect of extended prophylaxis was very modest and not even statistically significant in the primary cohort.
Taking into account that the vast majority of patients who reached the primary outcome had non-symptomatic venous thrombosis (of which the clinical relevance is still a matter of debate), the significance of these trial results for clinical practice is somewhat limited.
– Marcel Levi