Long-Term Effectiveness and Safety of Direct Oral Anticoagulants in Japanese Patients With Venous Thromboembolism ― Extended Follow-up Results From the KUROSIO Study ―

BACKGROUND: The KUROSIO study (UMIN000023747) previously demonstrated the efficacy and safety of direct oral anticoagulants (DOACs) over 52 weeks in patients with acute venous thromboembolism (VTE). However, the long-term outcomes of anticoagulation therapy in real-world practice remain unclear. METHODS AND RESULTS: We conducted a prespecified analysis with a 156-week clinical observation period. The primary efficacy outcome was symptomatic recurrent VTE, and the primary safety outcome was major bleeding at 156 weeks. Between September 2016 and November 2018, the study enrolled 1,017 patients, of whom 993 were eligible for analysis. The cumulative incidence of recurrent VTE and major bleeding at 52 weeks was 3.2% and 2.2%, respectively. The mean duration of DOAC therapy was 458.0 days. Symptomatic recurrent VTE occurred in 50 (5.0%) patients, including pulmonary embolism in 46 (4.6%) and deep vein thrombosis in 4 (0.4%). Major bleeding occurred in 26 (2.6%) patients. Multivariable analysis identified chemotherapy (hazard ratio [HR] 3.580) as a factor associated with recurrent VTE. For major bleeding, multivariable analysis identified lower baseline hemoglobin (HR 0.657), history of cerebral infarction (HR 7.250), and concomitant use of non-steroidal anti-inflammatory drugs other than aspirin at enrollment (HR 7.481) as significant risk factors. CONCLUSIONS: DOAC therapy showed sustained effectiveness and acceptable safety over 156 weeks in Japanese patients with VTE, supporting individualized decisions regarding treatment duration and bleeding risk.