Edoxaban Tosylate

The management of recurrent venous thromboembolism (VTE) despite anticoagulant treatment in patients with cancer is uncertain. To address this, we used data from the Hokusai VTE Cancer trial, which compared edoxaban with dalteparin to treat cancer-associated VTE.

To characterize and evaluate anticoagulant treatment strategies during and after on-treatment recurrent VTE, including the type and dose of anticoagulant.

In this post hoc analysis, all patients with adjudicated on-treatment recurrent VTE within 12 months after randomization were included. Outcomes were second recurrent VTE and major bleeding within 3 months after the first recurrent VTE.

A total of 67 patients developed on-treatment recurrent VTE while receiving therapeutic-dose edoxaban (31%), therapeutic-dose low-molecular-weight heparin (LMWH) (34%), maintenance-dose LMWH (21%), or other therapies (14%). After the recurrent event, 28 patients (42%) received an increased dose, 35 (52%) a comparable dose, and 4 (6%) a reduced dose or stopped anticoagulants. Common treatment regimens included supratherapeutic-dose LMWH (21%), therapeutic-dose LMWH (51%), direct oral anticoagulants (16%), or another treatment strategy (12%). In the 3 months after recurrent VTE, 6 (9%) patients had a second recurrence and 7 (10%) had major bleeding.

Treatment strategies for recurrent VTE in patients with cancer are heterogeneous. The risk of a second recurrence and major bleeding are considerable. More studies are needed to determine the optimal treatment strategy for recurrent cancer-associated thrombosis.

This study aimed to analyze differences in the exposure‐response relationship for factor Xa inhibitors (FXaI) between patients aged ≥ 80 and < 80 years. Patients with atrial fibrillation (AF) taking rivaroxaban, apixaban, or edoxaban were enrolled, and a single steady‐state trough concentration was measured. FXaI concentrations were compared with the expected range reported in clinical trials to define high or low drug levels. The primary outcome was major bleeding, and the secondary outcome was ischemic stroke or transient ischemic attack (IS/TIA). From 2016 to 2023, 1,037 patients aged from 30 to 105 years were enrolled (average, 75.4 ± 10.0 years; 33.8% were aged ≥ 80 years). During a median follow‐up of 2.35 years, 48 major bleeding events and 32 IS/TIA events were observed. Although drug concentrations were similar between the two age groups, those aged ≥ 80 years with high FXaI levels experienced a greater increase in major bleeding risk compared to those aged < 80 years with high levels (aHR 6.47 [2.07, 20.28] vs. 3.45 [1.15, 10.30]). Additionally, patients aged ≥ 80 years without elevated FXaI levels also had a higher risk of major bleeding compared to those aged < 80 years without elevated levels (aHR 2.39 [1.20, 4.76]). While low FXaI concentrations were associated with IS/TIA, the risk was not significantly different across age groups. In conclusion, despite similar FXaI concentrations, patients aged ≥ 80 years have a higher baseline risk of major bleeding and experience a greater increase in bleeding risk at high drug levels compared to those aged < 80 years.