Stopping anticoagulation based on negative D-dimer testing yielded a higher rate of VTE recurrence or major bleeding than reduced-dose apixaban (7.3% vs 1.1%; adjusted HR 8.2; 95% CI 3.2-25.3).
Cohort (n=732)
Yes
Does a D-dimer-guided strategy to stop anticoagulation increase the risk of VTE recurrence or major bleeding compared to extended reduced-dose apixaban in patients with unprovoked VTE?
D-dimer testing is inadequate to identify patients who can safely stop anticoagulation after unprovoked VTE, whereas extended treatment with reduced-dose apixaban is highly effective and safe.
Effect estimate: adjusted HR 8.2 (95% CI 3.2-25.3)
Absolute Event Rate: 7.3% vs 1.1%
D-dimer assay is used to stratify patients with unprovoked venous thromboembolism (VTE) for the risk of recurrence. However, this approach was never evaluated since direct oral anticoagulants are available. With this multicenter, prospective cohort study, we aimed to assess the value of an algorithm incorporating serial D-dimer testing and administration of reduced-dose apixaban (2.5 mg twice daily) only to patients with a positive test. A total of 732 outpatients aged 18 to 74 years, anticoagulated for ≥12 months after a first unprovoked VTE, were included. Patients underwent D-dimer testing with commercial assays and preestablished cutoffs. If the baseline D-dimer during anticoagulation was negative, anticoagulation was stopped and testing repeated after 15, 30, and 60 days. Patients with serially negative results (286 39.1%) were left without anticoagulation. At the first positive result, the remaining 446 patients (60.9%) were given apixaban for 18 months. All patients underwent follow-up planned for 18 months. The study was interrupted after a planned interim analysis for the high rate of primary outcomes (7.3%; 95% confidence interval CI, 4.5-11.2), including symptomatic proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) recurrence, death for VTE, and major bleeding occurring in patients off anticoagulation vs that in those receiving apixaban (1.1%; 95% CI, 0.4-2.6; adjusted hazard ratio HR, 8.2; 95% CI, 3.2-25.3). In conclusion, in patients anticoagulated for ≥1 year after a first unprovoked VTE, the decision to further extend anticoagulation should not be based on D-dimer testing. The results confirmed the high efficacy and safety of reduced-dose apixaban against recurrences. This trial was registered at www.clinicaltrials.gov as #NCT03678506.
Palareti et al. (Mon,) conducted a cohort in unprovoked venous thromboembolism (VTE) (n=732). Stopping anticoagulation (serially negative D-dimer) vs. Reduced-dose apixaban (positive D-dimer) was evaluated on symptomatic proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) recurrence, death for VTE, and major bleeding (adjusted HR 8.2, 95% CI 3.2-25.3). Stopping anticoagulation based on negative D-dimer testing yielded a higher rate of VTE recurrence or major bleeding than reduced-dose apixaban (7.3% vs 1.1%; adjusted HR 8.2; 95% CI 3.2-25.3).