Bleeding and Recurrence in Patients with Venous Thromboembolism with Changing Anticoagulant Treatment Patterns: Findings from the TROLL Registry

Abstract Treatment for venous thromboembolism (VTE) has shifted from vitamin K antagonists (VKAs) to direct oral anticoagulants (DOACs), with increased use of indefinite therapy. However, data on bleeding and recurrence outcomes associated with these changes remain limited. To evaluate the risk of major bleeding (MB), clinically relevant nonmajor bleeding (CRNMB), and recurrence with changing treatment patterns. Cancer-free VTE patients were identified in the Venous Thrombosis Registry in Østfold Hospital, Norway, from January 2005 to May 2020, and categorized into period 1 (2005–2012), period 2 (2013–2016), and period 3 (2017–2020). MB and CRNMB rates during anticoagulant treatment, and recurrence rates after anticoagulant discontinuation were assessed. Subhazard ratios (sHRs) were calculated using Fine-Gray analysis for time-period comparisons. Among 3,839 patients (48% female, median age: 67 years; IQR, 54–78), VKA use decreased from 76% in period 1 to 2% in period 3, while DOAC use increased from 1 to 85%. The MB rate ranged from 5.6 (95% confidence interval [CI]: 3.9–6.4) per 100 person-years in period 2 to 3.1 (2.3–4.2) in period 3. The CRNMB rate increased from 5.4 (95% CI: 4.3–6.9) per 100 person-years in period 1 to 7.7 (6.3–9.5) in period 3, sHR: 1.87 (1.36–2.56). Conversely, the recurrence rate decreased from 5.1 (95% CI: 4.6–5.6) per 100 person-years after anticoagulant discontinuation in period 1 to 3.9 (3.2–4.9) in period 3, sHR: 0.51 (0.41–0.65). VTE recurrences after anticoagulant discontinuation have declined, likely due to indefinite treatment in patients at high risk of recurrence, while CRNMB rates have increased over time.