Management of recurrent venous thromboembolism during anticoagulant treatment in patients with cancer: a prospective cohort study

Background: Recurrent venous thromboembolism (VTE) is a common complication in patients with cancer-associated VTE. Limited data are available on treatment, particularly in patients receiving direct oral anticoagulants (DOACs). We aimed to evaluate current management strategies and outcomes in patients with cancer and recurrent VTE during treatment with low-molecular-weight heparin (LMWH) or DOACs. Methods: This was an international, prospective, observational cohort study. Patients were treated according to local practice, though the study protocol encouraged the use of a dose escalation strategy in accordance with current clinical guidelines. Primary outcomes were second recurrent VTE and clinically relevant bleeding. Results: Between June 2020 and November 2024, 94 patients were enrolled, of whom 81 were included in the final analysis. At the time of recurrent VTE, 55% of patients were treated with a DOAC, 41% with therapeutic-dose LMWH, and 4% with maintenance-dose LMWH. Of DOAC patients, 51% switched to supratherapeutic-dose LMWH, 42% to therapeutic-dose LMWH, and 7% received other treatments. Of LMWH patients, 70% received dose escalation, 18% maintained the same dose, and 12% received other treatments. At 3-month follow-up, 10% had developed a second recurrence, 12% clinically relevant bleeding, and 20% died. VTE incidence was similar between patients receiving dose escalation and those maintained on therapeutic doses, while clinically relevant bleeding was more frequent in the latter (6% vs. 25%). Conclusions: The risk of second recurrent VTE was substantial despite two thirds of patients receiving dose escalation. Bleeding was common regardless of treatment intensity, underscoring the challenges in this patient population.