Key result
Stopping anticoagulation after negative D-dimer linked to over sevenfold higher recurrent VTE risk versus apixaban.
Why the study?
D-dimer assay is used to stratify recurrence risk in unprovoked VTE, but this approach had not been evaluated since direct oral anticoagulants became available.
Does serial D-dimer testing safely identify patients with unprovoked VTE who can discontinue anticoagulation compared to extending treatment with reduced-dose apixaban?
Cohort (n=732)
Open-label
Yes
Does serial D-dimer testing safely identify patients with unprovoked VTE who can discontinue anticoagulation compared to extending treatment with reduced-dose apixaban?
Hazard Ratio: 8.2 (95% CI 3.2–25.3)
Absolute Event Rate: 7.3% vs 1.1%
p-value: p=<0.001
In patients with unprovoked VTE treated for ≥12 months, serial D-dimer testing is inadequate for safely discontinuing anticoagulation, whereas extended therapy with reduced-dose apixaban is highly effective and safe.
Negative D-dimer testing should not guide anticoagulation discontinuation; challenges prior stratification and leaves open need for randomized confirmation in unprovoked VTE.
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.
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Palareti et al. (2022) conducted a cohort in Unprovoked venous thromboembolism (VTE) (n=732). Stopping anticoagulation (based on negative D-dimer) vs. Reduced-dose apixaban 2.5 mg twice daily (based on positive D-dimer) was evaluated on Composite of 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, p=<0.001). Stopping anticoagulation based on negative D-dimer testing in patients with unprovoked VTE resulted in a significantly higher rate of recurrent VTE and major bleeding compared to extended treatment with reduced-dose apixaban (adjusted HR 8.2).
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