D-dimer after 3 months of anticoagulation therapy and outcomes in cancer-associated isolated distal deep vein thrombosis

• Compared to a 3-month treatment, a 12-month edoxaban treatment is superior in reducing thrombotic events regardless of the D-dimer levels.

• A 12-month edoxaban treatment does not significantly increase the risk of major bleeding regardless of the D-dimer levels.

Cancer-associated isolated distal deep vein thrombosis (IDDVT) is a common complication in patients with cancer. The ONCO DVT study (NCT03895502) revealed the superiority of 12-month over 3-month edoxaban treatment with respect to thrombotic risk. However, it remains unclear whether D-dimer levels during anticoagulation influence the efficacy of extended anticoagulation. In this post-hoc subgroup analysis, we stratified 519 patients into the low D-dimer (<1.0 μg/mL) (N=308) and high D-dimer (≥1.0 μg/mL) (N=211) subgroups based on D-dimer levels at 3 months. The cumulative incidence of a composite of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death was lower in the 12-month edoxaban group than in the 3-month edoxaban group in both the low D-dimer (0.8% vs. 5.6%, P=0.02; odds ratio [OR], 0.12; 95% confidence interval [CI], 0.01–0.66) and high D-dimer (0.9% vs. 10.2%, P=0.01; OR, 0.11; 95% CI, 0.01–0.62) subgroups without interaction. Meanwhile, there was no significant difference in the cumulative incidence of major bleeding between the 12-month and 3-month groups in both the low D-dimer (3.6% vs. 1.8%, P=0.64; OR, 1.96; 95% CI, 0.47–9.67) and high D-dimer (18.3% vs. 14.6%, P=0.29; OR, 1.27; 95% CI, 0.60–2.75) subgroups without interaction. In conclusion, a 12-month edoxaban treatment for cancer-associated IDDVT was superior to a 3-month treatment in reducing thrombotic events, irrespective of D-dimer levels after 3 months of anticoagulation therapy. There was no significant increased risk of major bleeding in the 12-month edoxaban group relative to the 3-month edoxaban group regardless of the D-dimer levels at 3 months.