Risk of recurrence and bleeding in patients with cancer-associated venous thromboembolism in the direct oral anticoagulants era: Findings from the TULIPE registry

BACKGROUND: The introduction of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) treatment has led to their widespread adoption in clinical practice, potentially influencing management strategies and patient outcomes. However, real-world data on cancer-associated VTE in the DOAC era remain limited. This study aimed to evaluate the clinical characteristics and long-term outcomes of patients with cancer- and non-cancer-associated VTE in a real-world setting. METHODS: We retrospectively analyzed patients diagnosed with deep vein thrombosis (DVT) using lower-extremity venous ultrasound between January 2015 and August 2020 at the University of Tsukuba Hospital, a tertiary academic referral center in Japan. RESULTS: The cohort included 2,281 patients with DVT, comprising 1,152 with active cancer (cancer group) and 1,129 without cancer (non-cancer group). The cumulative 5-year incidence of recurrent VTE was significantly higher in the cancer group than in the non-cancer group (25% vs. 10%, P < 0.001). After adjusting for confounders and accounting for the competing risk of mortality, cancer remained a significant risk factor for recurrence (adjusted subdistribution hazard ratio [sHR]: 2.00; 95% confidence interval [CI]: 1.46-2.74). Similarly, the cumulative 5-year incidence of major bleeding was significantly higher in the cancer group (30% vs. 9.6%, P < 0.001). After adjustment, the risk of major bleeding remained significantly elevated in the cancer group compared to that in the non-cancer group (adjusted sHR: 2.69; 95% CI: 1.90-3.81). In the cancer group, discontinuation of bleeding-related anticoagulation therapy was associated with increased VTE recurrence (P < 0.001), whereas no such association was observed in the non-cancer group (P = 0.716). CONCLUSIONS: In the DOAC era, similar to the warfarin era, patients with cancer exhibited significantly higher rates of VTE recurrence and major bleeding than those without cancer.