Abstract
BACKGROUND: Cancer-associated thromboembolism has been thoroughly investigated in previous studies, and direct oral anticoagulants (DOACs) were established for the treatment and prevention of venous thromboembolism (VTE). However, the risks of cancer-associated arterial thromboembolism (ATE) and the efficacy of DOACs remain unclear. OBJECTIVES: To evaluate the risk factors and the clinical activity of edoxaban (EDO) for the prevention of ATE in patients with advanced lung cancer. METHODS: From the prospective Rising-VTE/NEJ037 study which investigated VTE in newly diagnosed advanced lung cancer, we investigated the incidence rate and the risk factors of ATE as secondary endpoints. RESULTS: A total of 1008 patients were screened for VTE at study baseline and were followed up for 2 years. Excluding patients with a contraindication to DOACs, those with VTE were treated with EDO. ATE events were identified in 41 patients (4.1%). The most common location for ATE was cerebral infarction (N = 31, 75.6%), followed by myocardial infarction (N = 4, 9.8%). Multivariate analysis determined the incidence of VTE, D-dimer, a comorbidity of atrial fibrillation, and four other factors as independent risk factors of ATE. For VTE (+) patients, the incidence rate of ATE was 15.9% for the EDO administration (+) patients, compared with 11.1% for the EDO administration (-) patients (p = 0.626). CONCLUSIONS: The incidence rate of ATE was 4.1% over 2-year follow-up in advanced lung cancer patients. VTE was further identified as an independent risk factor for ATE, while intervention with DOACs was seen as less effective for the prevention of ATE in advanced lung cancer patients with VTE. TRIAL REGISTRATION: This trial was registered in the Japan Registry of Clinical Trials (jRCTs061180025).