br Materials and methods Patients charts
Materials and methods Patients’ charts were reviewed retrospectively, and 165 consecutive patients (82 with cancer and 83 without cancer) who either started edoxaban (Lixiana®, Daiichi-Sankyo, Tokyo, Japan) therapy for the treatment of VTE or were switched from other oral anticoagulants to edoxaban for the treatment of VTE from September 2014 to September 2016 at Nagasaki University Hospital were initially recruited. VTE was confirmed by ultrasonography of the lower extremities, contrast-enhanced computed tomography, or magnetic resonance imaging. VTE was classified into 2 groups [deep vein thrombosis (DVT) and pulmonary thromboembolism (PE) with and without DVT], and the site of DVT was classified into 3 sites according to its location (between the inferior vena cava and knee joint as proximal DVT; below the knee joint as distal DVT; and between the Cdk2/Cyclin Inhibitory Peptide I and upper extremities as upper DVT). Hematological data from within 1 week before starting the administration of edoxaban or VTE occurrence were obtained. Active cancer was defined as a diagnosis of cancer within 6 months before edoxaban therapy, any treatment for cancer within the previous 6 months, or recurrent or metastatic cancer . To examine the direct effects of edoxaban in patients with and without cancer, patients who switched from warfarin to edoxaban for continuing anticoagulant therapy, those who stopped taking edoxaban within 1 week of commencement of its administration, and those who had non-active cancer were excluded. Finally, 125 patients (64 non-cancer and 61 cancer patients) were included in analyses of recurrence of VTE, clinically relevant bleeding, and death. Among them, 82 patients (48 non-cancer and 34 cancer patients) who underwent at least two imaging tests, such as ultrasonography of the lower extremities and contrast-enhanced computed tomography, before and after administration of edoxaban for more than 1 week and who had taken edoxaban for more than half of the duration between the two imaging tests were analyzed for the effects of edoxaban on changes in the amount of thrombosis (Fig. 1). Recurrence of VTE was defined as confirmed symptomatic recurrence of DVT or PE. Clinically relevant bleeding was defined as major or clinically relevant non-major bleeding according to previous papers . Major bleeding was defined if it was overt and was associated with a decrease in hemoglobin of 2g per deciliter or more, or required a transfusion of 2 or more units of blood, occurred at a critical site, or contributed to death. Clinically relevant non-major bleeding was defined as overt bleeding that did not meet the criteria for major bleeding, but was associated with the need for medical intervention, contact with a physician, interruption of the study drug, or with discomfort or impairment of activities of daily life. These events were examined during the administration of edoxaban. The occurrence of death was examined from the initiation of drug administration to February 28, 2017. When the status of survival or death was unknown, as in patients who transferred to other hospitals, they were defined as “uncertain”. Changes in the amount of thrombosis were classified as normalized (no thrombus in the legs and lungs), improved (improvements in both the legs and lungs, or improvement in either the legs or lungs without deterioration at the other site), unchanged (unchanged results for both legs and lungs), and deteriorated (any deterioration in either legs or lungs) , based on the judgment of radiologists, sonographers, and cardiologists. When the patients underwent more than two imaging tests after commencing edoxaban, the earliest test in which changes in VTE became stable was adopted as the post-treatment test.
Results The patients’ characteristics are shown in Table 1. Females were predominant in both the cancer and non-cancer groups. Average body weight was less than 60kg, and creatinine clearance levels were in the category of mild renal insufficiency. The approved doses of edoxaban for the treatment of VTE are 30mg and 60mg daily, with the choice depending on weight, renal function, and concomitant medications; in this study, more patients were taking the 30-mg daily dose. The d-dimer levels at the time of development of VTE were not significantly different in both groups (cancer 9.50μg/ml vs. non-cancer 6.90μg/ml, p=0.484). The duration of edoxaban therapy was not significantly different between the groups.